Affinage

CDC25C

M-phase inducer phosphatase 3 · UniProt P30307

Length
473 aa
Mass
53.4 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDC25C is a dual-specificity phosphatase that drives the G2/M transition by activating the cdc2(Cdk1)-cyclin B kinase, and its own phosphatase activity is in turn amplified through a positive feedback loop in which active cdc2-cyclin B phosphorylates CDC25C on multiple sites to increase its activity 2-3-fold and trigger premature mitotic entry (PMID:8428594, PMID:8119945). This autoamplification is held in check during interphase by PP2A, which keeps CDC25C dephosphorylated and inactive; the conformation-specific PP2A:B56δ holoenzyme, acting on trans pSer/Thr-Pro motifs generated by Pin1-catalyzed prolyl isomerization, restrains CDC25C and Cdk1 activity until mitotic exit (PMID:8389619, PMID:11090625, PMID:18056802). CDC25C activity and localization are governed by an extensive phosphorylation network: inhibitory phosphorylation of Ser216 by Chk1, Chk2, C-TAK1, and CaMKII creates a 14-3-3 binding site that enforces cytoplasmic retention by blocking nuclear import, working together with an intrinsic N-terminal nuclear export signal (PMID:9278512, PMID:9543386, PMID:11313932, PMID:14517314, PMID:12386164, PMID:10864927), while activating phosphorylation by Plk1/PLK on Ser198, by Plk3 on Ser191, and by ERK/MAPK on Thr48 overcomes nuclear exclusion and stimulates phosphatase activity at mitotic entry (PMID:11897663, PMID:11202906, PMID:14968113, PMID:17382881). This network couples CDC25C to checkpoint and stress signaling: DNA-damage and replication checkpoints converge on Ser216 phosphorylation and 14-3-3 sequestration to enforce G2 arrest (PMID:9278512, PMID:10681541), stress kinases such as JNK inactivate CDC25C, and oxidative stress drives an intramolecular disulfide bond that triggers degradation (PMID:11925443, PMID:12742231, PMID:20220133). CDC25C levels are further controlled by p53, which represses its transcription both by direct promoter binding and through the p21-dependent DREAM/CDE-CHR pathway, and by Mdm2, which promotes ubiquitin-independent proteasomal degradation, together enforcing G2/M arrest (PMID:15574328, PMID:28806397, PMID:26595675). Beyond mitotic control, CDC25C dephosphorylates the activation-loop Thr838 of ASK1 to suppress apoptosis during interphase, and a centrosomal pool co-localizes with cyclin B1 to locally amplify Cdk1 activation (PMID:25633196, PMID:18604163). Genetic ablation in mice shows CDC25C is dispensable for normal cell cycles, indicating functional redundancy with CDC25A/B (PMID:11359894, PMID:15767688).

Mechanistic history

Synthesis pass · year-by-year structured walk · 38 steps
  1. 1992 Medium

    Established that CDC25C is functionally required for cdc2 kinase activation and chromosome condensation, and that it is cytoplasmic in interphase but enters the nucleus upon checkpoint loss.

    Evidence Antibody microinjection in the tsBN2 (RCC1-mutant) genetic system with immunofluorescence localization

    PMID:1337289

    Open questions at the time
    • Mechanism of nuclear relocalization not defined
    • Substrate specificity for Cdk1 sites not yet mapped
  2. 1993 High

    Defined the core mitotic feedback loop: cdc2-cyclin B phosphorylation directly activates CDC25C, while PP2A keeps it inactive during interphase, framing the switch-like onset of mitosis.

    Evidence Xenopus egg extract and HeLa extract biochemistry with okadaic acid, PP2A catalytic subunit addition, and oocyte maturation assays

    PMID:8389619 PMID:8428594

    Open questions at the time
    • Specific activating phosphosites not yet mapped
    • Identity of the PP2A holoenzyme not defined
  3. 1994 High

    Mapped the cdc2-cyclin B activating phosphorylation to five sites and showed phosphorylation is functionally sufficient to drive premature prophase, defining the autoamplification mechanism.

    Evidence In vitro kinase assay, tryptic phosphopeptide mapping, peptide sequencing, microinjection into fibroblasts

    PMID:8119945

    Open questions at the time
    • Did not address how the loop is initially triggered
    • Spatial regulation not addressed
  4. 1994 Medium

    Biochemically purified an unidentified Ser216 kinase binding within aa 200-256, anticipating the regulatory checkpoint axis before its molecular identity was known.

    Evidence 8000-fold protein purification from rat liver with in vitro kinase assay and domain mapping

    PMID:7982962

    Open questions at the time
    • Kinase identity not molecularly defined at the time
    • Functional consequence of S216 phosphorylation not yet established
  5. 1997 High

    Connected the DNA-damage/replication checkpoint to CDC25C by showing Chk1 phosphorylates Ser216 to create a 14-3-3 site whose loss abrogates G2 arrest, establishing the checkpoint-CDC25C-14-3-3 axis.

    Evidence In vitro Chk1 kinase assay, S216A mutagenesis, and checkpoint abrogation assays

    PMID:9278512

    Open questions at the time
    • How 14-3-3 binding alters localization not yet resolved
    • Other Ser216 kinases not addressed
  6. 1998 High

    Identified C-TAK1 as a constitutive Ser216 kinase that directly binds CDC25C and promotes 14-3-3 binding, broadening the set of kinases enforcing cytoplasmic sequestration.

    Evidence In vitro kinase assay, Co-IP in COS-7 cells, bacterial co-expression, 14-3-3 binding assay

    PMID:9543386

    Open questions at the time
    • Physiological context distinguishing C-TAK1 from Chk1 not defined
  7. 1999 High

    Demonstrated that the 14-3-3-binding region (aa 201-258) mediates cytoplasmic retention and that disrupting 14-3-3 binding enables premature chromosome condensation, identifying 14-3-3 as the dominant interphase retention mechanism.

    Evidence Immunofluorescence with deletion/point mutagenesis, premature chromosome condensation assay, leptomycin B treatment

    PMID:10330186

    Open questions at the time
    • Relative contribution of NES not yet quantified
    • Mechanism by which 14-3-3 blocks import unresolved
  8. 1999 Medium

    Showed CaMKII phosphorylates and activates CDC25C and is required for G2/M progression, linking calcium signaling to mitotic entry.

    Evidence In vitro CaMKII kinase/phosphatase assay, HeLa synchronization, KN-93 and peptide inhibitor microinjection

    PMID:10075693

    Open questions at the time
    • Phosphosite not mapped in this study
    • Single lab
  9. 2000 High

    Resolved the import/export logic of CDC25C trafficking, showing an intrinsic N-terminal NES drives export while 14-3-3 binding negatively regulates nuclear import.

    Evidence Leptomycin B export inhibition, NES and 14-3-3-binding mutants, immunofluorescence

    PMID:11313932

    Open questions at the time
    • Import receptor not identified
    • How mitotic kinases override NES not yet addressed
  10. 2000 High

    Provided a structural basis for conformational regulation, showing the regulatory domain binds both 14-3-3 and cyclins and folds into helices upon 14-3-3 binding.

    Evidence NMR spectroscopy, circular dichroism, in vitro binding with purified 14-3-3 and cyclins

    PMID:10864927

    Open questions at the time
    • Full-length structure not solved
    • Functional consequence of cyclin P-box binding not defined
  11. 2000 High

    Introduced Pin1 prolyl isomerization as a conformational checkpoint that renders CDC25C competent for PP2A-mediated dephosphorylation, coupling proline-directed phosphorylation to phosphatase access.

    Evidence In vitro prolyl isomerase and conformation-specific PP2A assays, yeast genetic epistasis, in vivo cell division with Pin1 catalytic mutants

    PMID:11090625

    Open questions at the time
    • Specific isomerized motifs in CDC25C not fully enumerated
  12. 2000 High

    Linked the G2 checkpoint to therapy by showing UCN-01 inhibits Chk1-mediated Ser216 phosphorylation and abrogates 14-3-3 binding, validating the axis as a drug target.

    Evidence In vitro Chk1 kinase assay and IP of CDC25C/14-3-3 complexes from irradiated cells

    PMID:10681541

    Open questions at the time
    • Off-target kinase effects of UCN-01 not fully excluded
  13. 2000 Medium

    Established polo-like kinase as a direct activating kinase of CDC25C, increasing phosphatase activity toward cdc2-cyclin B.

    Evidence In vitro kinase assay with endogenous and recombinant PLK, phosphatase activity assay

    PMID:11202906

    Open questions at the time
    • Activating phosphosite not mapped here
    • In vivo requirement not established
  14. 2001 High

    Demonstrated in a cell-free meiotic system that polo-like kinase (Plx1) is necessary for Cdc25C and Cdc2 activation, establishing PLK as an upstream requirement.

    Evidence Immunodepletion of Plx1 from Xenopus oocyte extract with maturation assay

    PMID:11408585

    Open questions at the time
    • Direct vs. indirect requirement not separated
    • Mammalian generality from oocyte system
  15. 2001 High

    Showed via knockout that Cdc25C is dispensable for mouse development and cell cycles, revealing functional redundancy among CDC25 family members.

    Evidence Cdc25C knockout mouse with MEF cell cycle and DNA damage response analysis (confirmed by Cdc25B/C double-KO)

    PMID:11359894 PMID:15767688

    Open questions at the time
    • Degree of compensation by CDC25A/B not quantified
    • Cell-context-specific non-redundant roles not excluded
  16. 2002 High

    Refined the spatial activation step by showing Plk1 phosphorylates Ser198 within the NES to promote nuclear localization at prophase.

    Evidence In vitro kinase assay, S198A mutant, constitutively active Plk1, immunofluorescence

    PMID:11897663

    Open questions at the time
    • Interplay with 14-3-3 release not fully resolved
  17. 2002 High

    Established Chk2, in both monomeric and dimeric forms, as a DNA-damage-responsive CDC25C kinase, expanding the checkpoint kinase repertoire converging on CDC25C.

    Evidence Purification of Chk2 ± DNA damage, in vitro kinase assay on Cdc25C, biophysical sizing

    PMID:12386164

    Open questions at the time
    • In vivo site preference vs. Chk1 not distinguished
  18. 2002 Medium

    Identified arsenite-induced, KEN-box-dependent ubiquitin-proteasome degradation of CDC25C as a route to G2/M arrest, introducing proteolytic control of CDC25C abundance.

    Evidence Ubiquitination assay, proteasome inhibition, KEN-box mutagenesis and peptide competition

    PMID:11842186

    Open questions at the time
    • Responsible E3 ligase not identified
    • Physiological trigger beyond arsenite not defined
  19. 2002 Medium

    Discovered a physical CDC25C-PCNA interaction at the G2/M boundary, hinting at coupling to replication/repair machinery.

    Evidence Yeast two-hybrid, in vitro binding, Co-IP and co-localization in Jurkat cells

    PMID:11896603

    Open questions at the time
    • Functional consequence of the interaction not established
    • Single lab
  20. 2002 High

    Revealed redox control of CDC25C: H2O2 induces an active-site disulfide (C330-C377) that promotes degradation independently of Chk1, linking oxidative stress to CDC25C turnover.

    Evidence In vitro oxidation assay, C330/C377 mutants, stability and 14-3-3 binding assays

    PMID:11925443

    Open questions at the time
    • In vivo physiological oxidant source not defined
    • Link to ubiquitin machinery not resolved
  21. 2003 Medium

    Showed catalytically active CDC25C is required for human S-phase entry, extending its role beyond mitosis (in apparent contrast to mouse redundancy data).

    Evidence siRNA, antisense and antibody microinjection in HeLa, with wild-type vs. C377S rescue

    PMID:12857880

    Open questions at the time
    • Discrepancy with mouse KO redundancy unresolved
    • Relevant S-phase substrate not identified
  22. 2003 High

    Identified JNK/SAPK as a stress kinase that inactivates CDC25C via Ser168 phosphorylation, coupling stress signaling to mitotic inhibition.

    Evidence In vitro kinase assay, phospho-S168 detection, S168A rescue of cdc2-cyclin B activity (replicated)

    PMID:12742231 PMID:20220133

    Open questions at the time
    • Structural basis for S168-mediated inactivation unknown
  23. 2003 High

    Defined CaMKII Ser287 (Xenopus) phosphorylation as a calcium-triggered inhibitory event delaying Cdc2-cyclin B activation, mechanistically linking fertilization signals to cell cycle timing.

    Evidence Xenopus egg extract biochemistry, Ca2+ addition, CaMKII inhibitors, in vitro kinase assay

    PMID:14517314

    Open questions at the time
    • Mammalian equivalent site context not fully mapped
  24. 2003 Medium

    Showed Xp38γ/SAPK3 phosphorylates Cdc25C Ser205 to promote the meiotic G2/M transition independently of Mos/MAPK, adding a stress-kinase route to activation.

    Evidence Xenopus oocyte overexpression with CA/DN mutants, IP kinase assay, site identification

    PMID:14592973

    Open questions at the time
    • Mammalian relevance not established
    • Single lab
  25. 2004 High

    Established p53 as a transcriptional repressor of CDC25C through both direct promoter binding and a CDE/CHR-dependent route, placing CDC25C downstream of tumor suppressor signaling.

    Evidence Reporter assays with promoter mutations, EMSA, physiological p53 induction

    PMID:15574328

    Open questions at the time
    • Relative contribution of the two mechanisms not quantified at the time
  26. 2004 Medium

    Identified Plk3 as a kinase phosphorylating Ser191/Ser198 in the nuclear-exclusion motif, with phosphomimetics driving nuclear accumulation and reduced Cdc2-Y15.

    Evidence In vitro kinase assay, phosphomimetic/alanine mutagenesis, localization, Cdc2-Y15 western

    PMID:14968113

    Open questions at the time
    • Distinct roles of Plk1 vs. Plk3 on overlapping sites not reconciled
  27. 2004 Medium

    Showed Pim-1 activates CDC25C both directly by N-terminal phosphorylation and indirectly by inhibiting C-TAK1, adding an oncogenic kinase input to the activation network.

    Evidence Kinase assay, yeast two-hybrid, co-localization, MS site mapping, G2/M assay (two papers)

    PMID:15319445 PMID:16356754

    Open questions at the time
    • In vivo significance of dual mechanism not quantified
  28. 2005 Medium

    Demonstrated that HIV-1 Vpr binds CDC25C at a non-catalytic site to inhibit its phosphatase activity and drive viral G2 arrest, identifying CDC25C as a host target of viral cell cycle manipulation.

    Evidence In vitro binding and phosphatase inhibition, Co-IP, binding-deficient mutant and CDC25C depletion

    PMID:14972559

    Open questions at the time
    • Structural basis of inhibitory binding not solved
  29. 2007 High

    Established ERK/p42 MAPK as a major activating CDC25C kinase across systems, phosphorylating Thr48 (and T138/S205) to boost phosphatase activity and promote mitotic entry.

    Evidence Xenopus extract/oocyte biochemistry, Co-IP, in vitro kinase assay, site mapping, ERK inhibition in mammalian cells

    PMID:17382881

    Open questions at the time
    • Quantitative contribution relative to PLK feedback not defined
  30. 2007 High

    Identified PP2A:B56δ as the specific holoenzyme dephosphorylating CDC25C at interphase and mitosis, with its loss causing persistent Cdk1 activity and delayed mitotic exit, defining the molecular counterweight to the activation loop.

    Evidence Stable knockdown and mouse KO, biochemical phosphorylation analysis, mitotic timing, Wee1 compensation

    PMID:18056802

    Open questions at the time
    • Targeting mechanism of B56δ to CDC25C not defined
  31. 2007 Medium

    Showed LZTS1/Fez1 stabilizes Cdc25C during mitosis to sustain Cdk1 activity and proper chromosome segregation, identifying a scaffold protecting CDC25C from M-phase degradation.

    Evidence Lzts1 knockout mouse, MEF biochemistry, Cdc25C stability and Cdk1 activity assays, segregation analysis

    PMID:17349584

    Open questions at the time
    • Mechanism by which LZTS1 prevents degradation not defined
  32. 2008 Medium

    Revealed a centrosomal pool of CDC25C that co-localizes with cyclin B1 to locally amplify Cdk1 activation; phosphatase-dead mutants act as dominant negatives impairing mitotic entry.

    Evidence Immunofluorescence, FRAP, C-terminal domain mutants, dominant-negative assay

    PMID:18604163

    Open questions at the time
    • Centrosomal docking partner not identified
    • Single lab
  33. 2010 Medium

    Showed cyclin E/CDK2 phosphorylates CDC25C on Ser214 to cause premature activation, with LMW cyclin E driving CDC25C-dependent chromosomal instability, linking CDC25C to oncogenic cell cycle deregulation.

    Evidence Co-IP, in vitro kinase assay, phosphatase activity assay, CDC25C siRNA, segregation/centrosome analysis

    PMID:20530684

    Open questions at the time
    • Physiological role of S214 in normal cycle not defined
  34. 2012 Medium

    Integrated telomere dysfunction into the CDC25C axis, showing ATR/ATM-CHK1/2 signaling drives S216 phosphorylation, nuclear export, and degradation of CDC25C to sustain G2/M arrest, with p53 transcriptional input.

    Evidence TRF2/POT1 depletion, CHK1/2 and proteasome inhibition, phospho-S216 detection, checkpoint readout

    PMID:22842784

    Open questions at the time
    • E3 ligase for CDC25C degradation in this context not identified
  35. 2015 Medium

    Uncovered a non-mitotic role: CDC25C dephosphorylates ASK1 activation-loop Thr838 to suppress apoptosis during interphase, with hyperphosphorylated mitotic CDC25C releasing this inhibition.

    Evidence In vitro phosphatase assay on ASK1 pThr838, CDC25C siRNA/overexpression, Co-IP, ASK1 activity and apoptosis assays

    PMID:25633196

    Open questions at the time
    • In vivo significance of CDC25C-ASK1 axis not established
  36. 2015 Medium

    Refined p53-mediated repression to a p21-dependent DREAM-complex mechanism, showing DREAM replaces MMB at CDE/CHR elements with no detectable p53 promoter binding.

    Evidence ChIP, promoter reporter with CDE/CHR mutations, p21 knockdown epistasis

    PMID:26595675

    Open questions at the time
    • Reconciliation with earlier direct-p53-binding model not fully resolved
  37. 2017 Medium

    Identified Mdm2 as a p53-independent route to CDC25C downregulation, promoting ubiquitin-independent proteasomal degradation, completing a dual p53/Mdm2 mechanism for G2/M arrest.

    Evidence Co-IP, Mdm2 siRNA, half-life assay, proteasome inhibition, cell cycle timing

    PMID:28806397

    Open questions at the time
    • Structural basis of ubiquitin-independent degradation unknown
  38. 2023 Medium

    Added a post-transcriptional layer, showing the splicing factor PUF60 controls CDC25C exon 3 inclusion, with its loss triggering NMD and reduced CDC25C to impair G2/M and proliferation.

    Evidence Splicing factor screen in LUAD, PUF60 siRNA, RNA-seq splice variant detection, cell cycle analysis

    PMID:37682709

    Open questions at the time
    • Regulation of PUF60 activity toward CDC25C not defined
    • Generality beyond LUAD not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the dense, sometimes overlapping phosphorylation inputs (multiple activating and inhibitory kinases on shared sites) are temporally integrated to produce the switch-like CDC25C activation, and which E3 ligases mediate its various degradation routes.
  • No unified quantitative model of competing phosphorylation inputs
  • E3 ligases for checkpoint, arsenite, and Mdm2-associated degradation not all identified
  • Discrepancy between human S-phase requirement and mouse dispensability unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 4 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-5357801 Programmed Cell Death 1
Partners
CCNB1CDK1CHEK1CHEK2MDM2PCNAPLK1YWHAB

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CDC25C is phosphorylated on serine-216 throughout interphase (but not mitosis), and this phosphorylation mediates binding to 14-3-3 proteins. A S216A mutation abrogated 14-3-3 binding and allowed cells to escape G2 checkpoint arrest induced by unreplicated DNA or radiation. Chk1 phosphorylates CDC25C on serine-216 in vitro, establishing the checkpoint kinase–CDC25C–14-3-3 axis. In vitro kinase assay (Chk1 phosphorylation of CDC25C), site-directed mutagenesis (S216A), conditional overexpression, checkpoint abrogation assay Science High 9278512
1993 CDC25C phosphatase activity is directly activated by phosphorylation by the cdc2-cyclin B kinase in mitotic HeLa extracts and in vitro. Phosphorylation of CDC25C is required for activation of cdc2-cyclin B and entry into M-phase, establishing a positive feedback (autocatalytic) loop at the onset of mitosis. In vitro kinase/phosphatase assay, Xenopus egg extract activation assay, oocyte maturation assay, thiophosphorylation experiments The EMBO journal High 8428594
1993 PP2A (type-2A phosphatase) maintains CDC25C in a dephosphorylated, low-activity state during interphase in Xenopus egg extracts. Inhibition of PP2A by okadaic acid prevents CDC25C dephosphorylation and prematurely activates cdc2-cyclin B, while addition of PP2A catalytic subunit blocks kinase activation. This places PP2A as a negative regulator upstream of CDC25C in a positive feedback loop. Xenopus egg extract biochemistry, okadaic acid inhibition, PP2A catalytic subunit addition, phosphatase-specific inhibitors (inhibitor-2) Molecular biology of the cell High 8389619
1994 cdc2-cyclin B phosphorylates CDC25C on five specific sites in vitro and in vivo at the G2-M transition. Phosphorylation by cdc2-cyclin B increases CDC25C phosphatase activity 2–3-fold. Only phosphorylated CDC25C (not unphosphorylated) effectively induces premature prophase when microinjected into living fibroblasts, demonstrating that multisite phosphorylation by cdc2-cyclin B drives the autoamplification loop. In vitro kinase assay, tryptic phosphopeptide mapping, peptide sequencing, microinjection into living fibroblasts, phosphatase activity assay The Journal of biological chemistry High 8119945
1998 C-TAK1 (Cdc25C-associated protein kinase 1) phosphorylates CDC25C on serine-216 in vitro and in vivo. C-TAK1 physically interacts with CDC25C (co-immunoprecipitation in COS-7 cells). Co-production of C-TAK1 and CDC25C in bacteria results in stoichiometric S216 phosphorylation and facilitates 14-3-3 binding in vitro. In vitro kinase assay, co-immunoprecipitation, bacterial co-expression, 14-3-3 binding assay Cell growth & differentiation High 9543386
1999 CDC25C is retained in the cytoplasm during interphase in human cells. A 58-amino-acid region (aa 201–258) containing the 14-3-3 binding site is required for cytoplasmic localization. Mutations disrupting 14-3-3 binding cause pancellular redistribution and increased ability to induce premature chromosome condensation. Gamma irradiation or leptomycin B did not alter cytoplasmic localization, suggesting 14-3-3 binding (not NES) is the dominant mechanism for cytoplasmic retention during interphase. Monoclonal antibody immunofluorescence, deletion/point mutagenesis, premature chromosome condensation assay, leptomycin B treatment Molecular and cellular biology High 10330186
2000 14-3-3 binding regulates intracellular trafficking of CDC25C. CDC25C is actively exported from the nucleus via an intrinsic NES in its amino terminus. A 14-3-3-binding mutant of CDC25C is partially nuclear, and its nuclear accumulation is enhanced by leptomycin B. Loss of both NES function and 14-3-3 binding is required for complete nuclear accumulation. 14-3-3 binding negatively regulates nuclear import rather than promoting nuclear export. Leptomycin B nuclear export inhibition, NES mutation, 14-3-3-binding mutant, immunofluorescence localization Oncogene High 11313932
2000 Pin1 catalyzes prolyl isomerization of specific pSer/Thr-Pro motifs in CDC25C, facilitating their dephosphorylation by PP2A, which is conformation-specific and efficiently dephosphorylates only the trans pSer/Thr-Pro isomer. This Pin1-dependent isomerization is essential for cell division in vivo. In vitro prolyl isomerase assay, PP2A dephosphorylation assay with cis/trans-specific substrates, genetic epistasis in yeast, in vivo cell division assay with Pin1 catalytic mutants Molecular cell High 11090625
2002 Plk1 phosphorylates CDC25C on Ser198 within its nuclear export signal during prophase, promoting nuclear localization of CDC25C. A constitutively active Plk1 promotes nuclear accumulation; S198A mutant CDC25C remains cytoplasmic when wild-type CDC25C enters the nucleus during prophase. In vitro kinase assay, immunofluorescence microscopy, constitutively active Plk1 overexpression, S198A point mutation EMBO reports High 11897663
2000 Human PLK directly phosphorylates CDC25C in vitro (using endogenous PLK immunoprecipitated from G2/M-arrested Jurkat cells and recombinant PLK). Phosphorylation of CDC25C by PLK activates its phosphatase activity, as assessed by dephosphorylation of cdc2-cyclin B. In vitro kinase assay with endogenous and recombinant PLK, phosphatase activity assay Cellular signalling Medium 11202906
2001 Immunodepletion of Plx1 (Xenopus polo-like kinase) from oocyte extracts completely inhibited activation of Cdc25C and cyclin B-Cdc2 by PKI, demonstrating that Plx1 is necessary for Cdc25C activation during meiotic maturation. Immunodepletion from Xenopus oocyte extract, cell-free maturation assay with PKI, MAPK pathway inhibition Molecular biology of the cell High 11408585
2000 UCN-01 causes loss of CDC25C serine-216 phosphorylation and 14-3-3 binding in DNA-damaged cells. UCN-01 potently inhibits Chk1-mediated phosphorylation of CDC25C in vitro, identifying Chk1 and the CDC25C pathway as targets of UCN-01-mediated G2 checkpoint abrogation. In vitro Chk1 kinase assay, immunoprecipitation of CDC25C/14-3-3 complexes from irradiated cells, phosphorylation-site western blot The Journal of biological chemistry High 10681541
1994 A serine kinase that associates with and phosphorylates CDC25C on serine-216 was purified ~8000-fold from rat liver as a 36–38 kDa doublet. The kinase binds within amino acids 200–256 of CDC25C, a region that also contains a putative bipartite nuclear localization signal. Protein purification (8000-fold), in vitro kinase assay, domain mapping The Journal of biological chemistry Medium 7982962
2002 Hydrogen peroxide induces an intramolecular disulfide bond between the active-site cysteine (C377) and C330 in CDC25C in vitro, promoting its degradation in vivo. A double C330/C377 mutant that cannot form this disulfide is more stable, resistant to oxidative stress-induced degradation, and shows reduced 14-3-3 binding in vitro and in vivo. Chk1 phosphorylation site mutation did not prevent H2O2-induced degradation, indicating a Chk1-independent mechanism. In vitro oxidation assay, site-directed mutagenesis (C330A, C377A, double mutant), stability/half-life assay, 14-3-3 binding assay The Journal of biological chemistry High 11925443
2004 Plk3 phosphorylates CDC25C primarily on S191 (and to a lesser extent S198) in vitro; both sites are within the nuclear exclusion motif. The S191D phosphomimetic mutant accumulates in the nucleus, whereas S191A facilitates nuclear exclusion. Plk3 overexpression promotes CDC25C nuclear accumulation and decreased Cdc2 Y15 phosphorylation; kinase-dead Plk3 fails to do so. In vitro kinase assay, phosphomimetic/alanine mutagenesis, immunofluorescence localization, Cdc2 Y15 phosphorylation western blot Oncogene Medium 14968113
2007 ERK2/p42 MAPK is a major Cdc25C-phosphorylating kinase in M-phase-arrested Xenopus egg extracts. In Xenopus oocytes, p42 MAPK interacts with hypophosphorylated Cdc25C before meiotic induction and phosphorylates Cdc25C at T48, T138, and S205, increasing its phosphatase activity. In mammalian cells, ERK1/2 interacts with Cdc25C in interphase and phosphorylates Cdc25C at T48 in mitosis; ERK inhibition partially inhibits T48 phosphorylation, Cdc25C activation, and mitotic entry. Xenopus egg extract biochemistry, co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, ERK inhibition in mammalian cells Cell High 17382881
2003 JNK/SAPK directly phosphorylates CDC25C on serine-168 in vitro. S168 is phosphorylated in vivo in response to stress (UV, DNA damage). Phospho-S168 CDC25C lacks phosphatase activity; S168A mutant expression reverses JNK-mediated inhibition of cdc2-cyclin B kinase activity. In vitro kinase assay, phosphospecific antibody detection in vivo, S168A mutagenesis, cdc2-cyclin B activity assay Cellular signalling High 12742231 20220133
2003 CaMKII phosphorylates Cdc25C on S287 in vitro and delays Cdc2-cyclin B activation via S287 phosphorylation in Xenopus egg extracts. S287-kinase activity is stimulated upon Ca2+ addition (mimicking fertilization) and is dependent on CaMKII; it is not dependent on cyclin B degradation or Cdc2 inactivation. Xenopus egg extract biochemistry, Ca2+ addition assay, CaMKII-specific inhibitors (KN-93, UCN-01, debromohymenialdisine), in vitro CaMKII kinase assay on Cdc25C Molecular biology of the cell High 14517314
1999 CaM kinase II phosphorylates CDC25C in vitro and increases its phosphatase activity 2.5–3-fold. Inhibition of CaM kinase II in synchronized HeLa cells (KN-93 or microinjected AC3-I peptide) causes G2 block with unphosphorylated CDC25C, phosphorylated Cdc2-Y15, and no histone H1 kinase activation. In vitro CaM kinase II kinase/phosphatase assay, HeLa cell synchronization, KN-93 pharmacological inhibition, microinjection of peptide inhibitor The Journal of biological chemistry Medium 10075693
2002 Chk2 monomers and dimers both phosphorylate Cdc25C in vitro. Chk2 from unstressed cells is largely monomeric, inactive, and unphosphorylated at Thr-68. After DNA damage, active Chk2 exists as stable Thr-68-phosphorylated dimers as well as Thr-68-unphosphorylated monomers/dimers, all capable of phosphorylating Cdc25C. Purification of Chk2 from baculovirus-infected insect cells and human cells ± DNA damage, in vitro kinase assay with Cdc25C substrate, Stokes radius and sedimentation coefficient analysis The Journal of biological chemistry High 12386164
2004 Pim-1 kinase directly binds and phosphorylates the N-terminal region of CDC25C, enhancing its phosphatase activity. Pim-1 also phosphorylates and inhibits C-TAK1 (which normally phosphorylates and inactivates CDC25C), thus indirectly activating CDC25C through two mechanisms. Pim-1 and CDC25C co-localize in the cytoplasm. Biochemical kinase assay, yeast two-hybrid, immunofluorescence co-localization, mass spectrometry of phosphorylation sites, G2/M progression assay The Journal of biological chemistry / The international journal of biochemistry & cell biology Medium 15319445 16356754
1999 Prk (a polo-related kinase) physically interacts with CDC25C and phosphorylates it at two sites in vitro, with the major site co-migrating with serine-216. Co-immunoprecipitation and affinity chromatography confirmed the interaction. Prk-phosphorylated CDC25C showed enhanced kinase activity. Baculovirus expression, in vitro kinase assay, co-immunoprecipitation, affinity column chromatography, phosphopeptide mapping Oncogene Medium 10557092
2000 An essential phosphorylation-site domain of CDC25C (aa ~200–256) interacts with both 14-3-3 proteins and cyclins (via the cyclin P-box motif). NMR and circular dichroism reveal two alpha-helical moieties interconnected by a loop carrying the 14-3-3 binding site; helical folding is induced upon 14-3-3 binding, suggesting conformational regulation. NMR spectroscopy, circular dichroism, in vitro binding assays with purified 14-3-3 and cyclins, domain analysis The Journal of biological chemistry High 10864927
2002 Arsenite induces CDC25C degradation via the ubiquitin-proteasome pathway. Mutation of the KEN box within residues 151–157 of CDC25C, or competition with a KEN-box peptide, partially inhibits arsenite-induced CDC25C ubiquitination. This CDC25C degradation contributes to G2/M arrest. Ubiquitination assay, proteasome inhibition, KEN-box mutagenesis, KEN-box peptide competition Proceedings of the National Academy of Sciences of the United States of America Medium 11842186
2004 p53 represses CDC25C transcription via two independent mechanisms: (1) direct binding of p53 to a site in the cdc25C promoter; (2) a CDE/CHR element-dependent mechanism not requiring p53 direct binding. Three CCAAT elements previously implicated do not mediate repression at physiologically relevant p53 levels. Reporter gene assay with promoter mutations, p53 binding site mutation, gel shift/EMSA, cell-based p53 induction at physiological levels Molecular cell High 15574328
2002 CDC25C interacts with PCNA, as identified by yeast two-hybrid and confirmed by in vitro and in vivo co-immunoprecipitation. CDC25C and PCNA transiently co-immunoprecipitate and co-localize in the nucleus at the beginning of M phase in Jurkat cells. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation from Jurkat cells, immunofluorescence co-localization Oncogene Medium 11896603
2007 PP2A:B56δ dephosphorylates CDC25C both during interphase and at mitosis. Loss of PP2A:B56δ (stable knockdown or mouse KO) results in prolonged CDC25C hyperphosphorylation/activation and persistent Cdk1 activation, causing delayed mitotic exit. This is compensated by transcriptional upregulation of Wee1 kinase. Stable knockdown, mouse knockout, biochemical analysis of CDC25C and Cdk1 phosphorylation, mitotic timing assay, Wee1 expression analysis Proceedings of the National Academy of Sciences of the United States of America High 18056802
2003 Xp38γ/SAPK3 phosphorylates Xenopus Cdc25C on Ser205 and promotes meiotic G2/M transition. Overexpression of constitutively active MKK6-Xp38γ induces oocyte maturation without progesterone; kinase-dead MKK6 and Xp38γ inhibit progesterone-induced maturation. This requires neither Mos/MAPK nor protein synthesis. Xenopus oocyte overexpression, constitutively active/dominant-negative mutants, immunoprecipitation kinase assay, site identification The EMBO journal Medium 14592973
2001 Cdc25C knockout mice are viable, fertile, and display no obvious abnormalities. MEFs lacking Cdc25C show normal cdc2 phosphorylation, normal timing of mitotic entry, and normal DNA damage responses. This demonstrates Cdc25C is dispensable for embryonic and adult cell cycles in mice, suggesting functional redundancy with Cdc25A and/or Cdc25B. Mouse gene knockout, MEF cell cycle analysis, DNA damage response assay, tissue expression analysis Molecular and cellular biology High 11359894 15767688
2003 CDC25C functional phosphatase activity is required for S-phase entry in human cells. CDC25C protein and activity increase at S-phase onset. Antisense, siRNA, or microinjection of anti-CDC25C antibodies inhibits DNA synthesis; re-introduction of wild-type but not catalytically-dead (C377S) CDC25C restores normal cell cycle progression. siRNA knockdown, antisense microinjection, immunoprecipitate phosphatase activity assay from synchronized HeLa cells, wild-type vs. C377S rescue Molecular biology of the cell Medium 12857880
2007 LZTS1/Fez1 interacts with Cdk1 and Cdc25C during mitosis. In Lzts1−/− MEFs, Cdc25C degradation is increased during M phase, resulting in decreased Cdk1 activity, accelerated mitotic progression, resistance to taxol/nocodazole-induced M-phase arrest, and improper chromosome segregation. Lzts1 knockout mouse, MEF biochemical analysis, Cdc25C stability assay, Cdk1 activity assay, chromosome segregation analysis Cancer cell Medium 17349584
2012 Telomere damage (via TRF2 or POT1 depletion) activates ATR/ATM, which phosphorylate CHK1/CHK2, leading to S216 phosphorylation of CDC25C, its nuclear export, and proteasomal degradation. This CDC25C degradation is required to sustain G2/M arrest from dysfunctional telomeres. Additionally, p53 transcriptionally downregulates CDC25C in this context. TRF2/POT1 siRNA depletion, CHK1/2 inhibition, proteasome inhibition, phospho-S216 CDC25C detection, checkpoint abrogation readout The EMBO journal Medium 22842784
2017 Mdm2 physically interacts with CDC25C and promotes its proteasomal degradation in a ubiquitin-independent manner, reducing CDC25C half-life. Either Mdm2 overexpression or CDC25C downregulation delays cell cycle progression through G2/M. This is a p53-independent pathway, providing a dual mechanism (p53-mediated transcriptional repression + Mdm2-mediated protein degradation) for p53/Mdm2 to enforce G2/M arrest. Co-immunoprecipitation, Mdm2 siRNA, half-life assay, proteasome inhibition, cell cycle timing analysis Oncogene Medium 28806397
2015 During interphase, CDC25C phosphatase dephosphorylates phospho-Thr-838 in the activation loop of ASK1, suppressing ASK1-mediated apoptosis. CDC25C knockdown increases ASK1 activity; CDC25C overexpression inhibits ASK1-mediated apoptosis. During mitotic arrest, hyperphosphorylated CDC25C has reduced affinity for ASK1, allowing increased ASK1 activity. This reveals a cell cycle-dependent role for CDC25C in suppressing apoptosis during interphase. In vitro phosphatase assay (CDC25C on ASK1 pThr-838), siRNA knockdown of CDC25C, co-immunoprecipitation, ASK1 activity assay, apoptosis assay Cell death and differentiation Medium 25633196
2008 A fraction of CDC25C localizes to centrosomes in a cell cycle-dependent manner from late S phase through mitosis. CDC25C co-localizes with Cyclin B1 at centrosomes in G2 and prophase, and both undergo dynamic exchange between centrosome and cytoplasm (FRAP). Centrosomal localization is mediated by the catalytic C-terminal domain but does not require catalytic activity. Phosphatase-dead and substrate-binding mutants of CDC25C accumulate at centrosomes with phospho-Y15-Cdk1 and behave as dominant negatives that impair mitotic entry. Immunofluorescence, FRAP live-cell imaging, C-terminal domain deletion/mutant analysis, phosphatase-dead and hotspot mutants, dominant-negative assay Cell cycle Medium 18604163
2010 Cyclin E/CDK2 physically interacts with and phosphorylates CDC25C on Ser214, leading to premature CDC25C activation. Low molecular weight (LMW) cyclin E overexpression causes premature inactivation of CDC25C and PLK1, leading to faster mitotic exit. Downregulation of CDC25C inhibits LMW-E-mediated chromosome missegregation, anaphase bridges, and centrosome amplification. Co-immunoprecipitation, in vitro kinase assay, CDC25C phosphatase activity assay, siRNA knockdown of CDC25C, chromosome segregation/centrosome analysis Cancer research Medium 20530684
2005 HIV-1 Vpr directly binds CDC25C in vitro and in mammalian cells and inhibits CDC25C phosphatase activity in vitro by binding a site distinct from the catalytic site. Expression of a Cdc25C mutant with reduced Vpr binding or siRNA depletion of Cdc25C reduces Vpr-mediated G2 arrest. In vitro binding assay, co-immunoprecipitation from mammalian cells, in vitro phosphatase inhibition assay, CDC25C mutant with reduced Vpr binding, CDC25C depletion Virology Medium 14972559
1992 Microinjected antibody to hamster/human CDC25C inhibits chromosome condensation induced by loss of RCC1 function (tsBN2 mutation), demonstrating that CDC25C is required for p34cdc2 kinase activation in this context. CDC25C is located predominantly in the cytoplasm (periphery of nuclei) in interphase cells and moves into the nucleus upon loss of RCC1 function. Antibody microinjection, tsBN2 cell genetic system, immunofluorescence localization Molecular biology of the cell Medium 1337289
2015 p53-dependent repression of CDC25C requires activation of p21 (CDKN1A), which causes replacement of the MMB (B-MYB-MuvB) complex by the DREAM complex at CDE/CHR elements in the CDC25C promoter. ChIP shows E2F4 and p130 (DREAM components) replace B-MYB upon p53 activation; mutations in CDE/CHR elements abolish p53-dependent repression. No p53 binding to the CDC25C promoter is detected by ChIP. Chromatin immunoprecipitation (ChIP), promoter reporter assays with CDE/CHR mutations, p21 knockdown epistasis Oncotarget Medium 26595675
2023 PUF60, a poly(U)-binding splicing factor, controls alternative splicing of CDC25C. PUF60 knockdown causes exon 3 skipping in CDC25C, leading to nonsense-mediated mRNA decay and decreased CDC25C protein, thereby inhibiting G2/M transition and cancer cell proliferation. Systematic splicing factor analysis in LUAD, siRNA knockdown of PUF60, RNA-seq for splice variant detection, cell cycle analysis Cell reports Medium 37682709

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science (New York, N.Y.) 1195 9278512
1993 Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis. The EMBO journal 586 8428594
2000 The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01. The Journal of biological chemistry 486 10681541
2000 Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins. Molecular cell 474 11090625
2000 Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25C. Current opinion in cell biology 318 11063929
1995 Cell cycle regulation of the cyclin A, cdc25C and cdc2 genes is based on a common mechanism of transcriptional repression. The EMBO journal 292 7556094
2002 Plk1 promotes nuclear translocation of human Cdc25C during prophase. EMBO reports 274 11897663
1999 Cytoplasmic localization of human cdc25C during interphase requires an intact 14-3-3 binding site. Molecular and cellular biology 242 10330186
2020 The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review. Cancer cell international 233 32518522
1998 C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 214 9543386
2002 Redox regulation of Cdc25C. The Journal of biological chemistry 188 11925443
2000 The human polo-like kinase, PLK, regulates cdc2/cyclin B through phosphorylation and activation of the cdc25C phosphatase. Cellular signalling 177 11202906
1993 Dephosphorylation of cdc25-C by a type-2A protein phosphatase: specific regulation during the cell cycle in Xenopus egg extracts. Molecular biology of the cell 176 8389619
2001 Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding. Oncogene 166 11313932
2000 NF-Y mediates the transcriptional inhibition of the cyclin B1, cyclin B2, and cdc25C promoters upon induced G2 arrest. The Journal of biological chemistry 158 11096075
2001 Absence of apparent phenotype in mice lacking Cdc25C protein phosphatase. Molecular and cellular biology 149 11359894
1999 Cdc25B and Cdc25C differ markedly in their properties as initiators of mitosis. The Journal of cell biology 145 10444066
2001 The polo-like kinase Plx1 is required for activation of the phosphatase Cdc25C and cyclin B-Cdc2 in Xenopus oocytes. Molecular biology of the cell 142 11408585
2004 DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: one involves direct binding to the cdc25C promoter. Molecular cell 134 15574328
1994 Activation of p34cdc2 protein kinase by microinjection of human cdc25C into mammalian cells. Requirement for prior phosphorylation of cdc25C by p34cdc2 on sites phosphorylated at mitosis. The Journal of biological chemistry 127 8119945
2005 Resveratrol causes Cdc2-tyr15 phosphorylation via ATM/ATR-Chk1/2-Cdc25C pathway as a central mechanism for S phase arrest in human ovarian carcinoma Ovcar-3 cells. Carcinogenesis 125 15975956
2004 Regulation of Cdc25C activity during the meiotic G2/M transition. Cell cycle (Georgetown, Tex.) 123 15136768
2004 The oncogenic serine/threonine kinase Pim-1 phosphorylates and inhibits the activity of Cdc25C-associated kinase 1 (C-TAK1): a novel role for Pim-1 at the G2/M cell cycle checkpoint. The Journal of biological chemistry 123 15319445
1999 Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells. The Journal of biological chemistry 121 10075693
2005 Normal cell cycle and checkpoint responses in mice and cells lacking Cdc25B and Cdc25C protein phosphatases. Molecular and cellular biology 120 15767688
2018 Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells. Nature communications 116 30097580
1996 Regulation of the acquisition of meiotic competence in the mouse: changes in the subcellular localization of cdc2, cyclin B1, cdc25C and wee1, and in the concentration of these proteins and their transcripts. Journal of cell science 113 8886990
2007 Regulation of Cdc25C by ERK-MAP kinases during the G2/M transition. Cell 112 17382881
2005 The oncogenic serine/threonine kinase Pim-1 directly phosphorylates and activates the G2/M specific phosphatase Cdc25C. The international journal of biochemistry & cell biology 107 16356754
1994 Role of the cdc25C phosphatase in G2 arrest induced by nitrogen mustard. Proceedings of the National Academy of Sciences of the United States of America 100 7937793
2006 Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells. Molecular cancer therapeutics 99 17172433
1998 UCN-01 abrogates G2 arrest through a Cdc2-dependent pathway that is associated with inactivation of the Wee1Hu kinase and activation of the Cdc25C phosphatase. The Journal of biological chemistry 95 9837924
1995 Cell cycle regulation of cdc25C transcription is mediated by the periodic repression of the glutamine-rich activators NF-Y and Sp1. Nucleic acids research 92 7479023
1995 Periodic cdc25C transcription is mediated by a novel cell cycle-regulated repressor element (CDE). The EMBO journal 90 7828585
2002 Abrogation of the S phase DNA damage checkpoint results in S phase progression or premature mitosis depending on the concentration of 7-hydroxystaurosporine and the kinetics of Cdc25C activation. The Journal of biological chemistry 87 11953432
2013 Inhibition of protein phosphatase 2A radiosensitizes pancreatic cancers by modulating CDC25C/CDK1 and homologous recombination repair. Clinical cancer research : an official journal of the American Association for Cancer Research 86 23780887
2002 Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences of the United States of America 77 11842186
2000 Acquisition of meiotic competence in mouse oocytes: absolute amounts of p34(cdc2), cyclin B1, cdc25C, and wee1 in meiotically incompetent and competent oocytes. Biology of reproduction 77 11090427
2007 Control of mitotic exit by PP2A regulation of Cdc25C and Cdk1. Proceedings of the National Academy of Sciences of the United States of America 75 18056802
1994 Purification of a serine kinase that associates with and phosphorylates human Cdc25C on serine 216. The Journal of biological chemistry 73 7982962
2012 ATM/ATR checkpoint activation downregulates CDC25C to prevent mitotic entry with uncapped telomeres. The EMBO journal 72 22842784
2016 Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells. Biochemical pharmacology 71 28012958
2003 Functional cdc25C dual-specificity phosphatase is required for S-phase entry in human cells. Molecular biology of the cell 68 12857880
2014 Recurrent CDC25C mutations drive malignant transformation in FPD/AML. Nature communications 67 25159113
2005 Hsp90 inhibitors cause G2/M arrest associated with the reduction of Cdc25C and Cdc2 in lung cancer cell lines. Journal of cancer research and clinical oncology 67 16283383
2010 JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G(2)/M DNA damage checkpoint. The Journal of biological chemistry 66 20220133
2002 Checkpoint kinase 2 (Chk2) monomers or dimers phosphorylate Cdc25C after DNA damage regardless of threonine 68 phosphorylation. The Journal of biological chemistry 66 12386164
2001 Effects of genistein on cell proliferation and cell cycle arrest in nonneoplastic human mammary epithelial cells: involvement of Cdc2, p21(waf/cip1), p27(kip1), and Cdc25C expression. Biochemical pharmacology 66 11286989
1992 Chromosome condensation caused by loss of RCC1 function requires the cdc25C protein that is located in the cytoplasm. Molecular biology of the cell 66 1337289
2004 Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation. Oncogene 65 14968113
2004 Many fingers on the mitotic trigger: post-translational regulation of the Cdc25C phosphatase. Cell cycle (Georgetown, Tex.) 64 14657664
2005 Increased expression and activity of CDC25C phosphatase and an alternatively spliced variant in prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 62 16000564
2006 DNA damage-induced down-regulation of human Cdc25C and Cdc2 is mediated by cooperation between p53 and maintenance DNA (cytosine-5) methyltransferase 1. The Journal of biological chemistry 61 16807237
2005 Vpr protein of human immunodeficiency virus type 1 binds to 14-3-3 proteins and facilitates complex formation with Cdc25C: implications for cell cycle arrest. Journal of virology 61 15708996
2007 Inhibition of Hsp90 function by ansamycins causes downregulation of cdc2 and cdc25c and G(2)/M arrest in glioblastoma cell lines. Oncogene 60 17525741
2007 Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development. Cancer cell 58 17349584
2003 Genistein activates p38 mitogen-activated protein kinase, inactivates ERK1/ERK2 and decreases Cdc25C expression in immortalized human mammary epithelial cells. The Journal of nutrition 57 12514295
2019 Induction of G2/M Phase Arrest by Diosgenin via Activation of Chk1 Kinase and Cdc25C Regulatory Pathways to Promote Apoptosis in Human Breast Cancer Cells. International journal of molecular sciences 56 31881805
1999 The physical association and phosphorylation of Cdc25C protein phosphatase by Prk. Oncogene 56 10557092
2015 Indirect p53-dependent transcriptional repression of Survivin, CDC25C, and PLK1 genes requires the cyclin-dependent kinase inhibitor p21/CDKN1A and CDE/CHR promoter sites binding the DREAM complex. Oncotarget 55 26595675
2002 Cdc25C interacts with PCNA at G2/M transition. Oncogene 54 11896603
1996 Endoreplication in megakaryoblastic cell lines is accompanied by sustained expression of G1/S cyclins and downregulation of cdc25C. Oncogene 54 8761290
2016 Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1. American journal of translational research 53 28077999
2017 Parvovirus B19 NS1 protein induces cell cycle arrest at G2-phase by activating the ATR-CDC25C-CDK1 pathway. PLoS pathogens 52 28264028
2001 Expression of the cell cycle phosphatase cdc25C is down-regulated by the tumor suppressor protein p53 but not by p73. Biochemical and biophysical research communications 52 11396965
2013 Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathway. Oncology reports 45 24002546
2004 The human immunodeficiency virus Vpr protein binds Cdc25C: implications for G2 arrest. Virology 44 14972559
2021 ESRRA promotes gastric cancer development by regulating the CDC25C/CDK1/CyclinB1 pathway via DSN1. International journal of biological sciences 43 34131395
2016 miR-142-3p inhibits cancer cell proliferation by targeting CDC25C. Cell proliferation 43 26805039
2017 Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase. Oncogene 42 28806397
2014 Inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through upregulating CDC25C expression. Carcinogenesis 42 24626146
2003 Xp38gamma/SAPK3 promotes meiotic G(2)/M transition in Xenopus oocytes and activates Cdc25C. The EMBO journal 42 14592973
2000 Alternative splicing in the regulatory region of the human phosphatases CDC25A and CDC25C. European journal of cell biology 42 11139144
2002 A single cell cycle genes homology region (CHR) controls cell cycle-dependent transcription of the cdc25C phosphatase gene and is able to cooperate with E2F or Sp1/3 sites. Nucleic acids research 41 11972334
2023 PUF60 promotes cell cycle and lung cancer progression by regulating alternative splicing of CDC25C. Cell reports 40 37682709
2010 Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes. BMC cancer 40 20500813
2007 Theaflavins induce G2/M arrest by modulating expression of p21waf1/cip1, cdc25C and cyclin B in human prostate carcinoma PC-3 cells. Life sciences 40 17936851
2006 p14ARF triggers G2 arrest through ERK-mediated Cdc25C phosphorylation, ubiquitination and proteasomal degradation. Cell cycle (Georgetown, Tex.) 40 16582626
2018 Radiosensitization by irinotecan is attributed to G2/M phase arrest, followed by enhanced apoptosis, probably through the ATM/Chk/Cdc25C/Cdc2 pathway in p53-mutant colorectal cancer cells. International journal of oncology 39 30085332
2013 UCN-01 induces S and G2/M cell cycle arrest through the p53/p21(waf1) or CHK2/CDC25C pathways and can suppress invasion in human hepatoma cell lines. BMC cancer 39 23537372
2018 The new 6q27 tumor suppressor DACT2, frequently silenced by CpG methylation, sensitizes nasopharyngeal cancer cells to paclitaxel and 5-FU toxicity via β-catenin/Cdc25c signaling and G2/M arrest. Clinical epigenetics 38 30359298
2015 Cell cycle-dependent Cdc25C phosphatase determines cell survival by regulating apoptosis signal-regulating kinase 1. Cell death and differentiation 38 25633196
2003 SAPK/JNK regulates cdc2/cyclin B kinase through phosphorylation and inhibition of cdc25c. Cellular signalling 37 12742231
2003 Regulation of Cdc2/cyclin B activation in Xenopus egg extracts via inhibitory phosphorylation of Cdc25C phosphatase by Ca(2+)/calmodulin-dependent protein [corrected] kinase II. Molecular biology of the cell 37 14517314
2014 Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM-Chk1/2-Cdc25C pathway. Toxicology and applied pharmacology 36 25450480
2011 Reactive-oxygen-species-mediated Cdc25C degradation results in differential antiproliferative activities of vanadate, tungstate, and molybdate in the PC-3 human prostate cancer cell line. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 36 22012316
2000 An essential phosphorylation-site domain of human cdc25C interacts with both 14-3-3 and cyclins. The Journal of biological chemistry 36 10864927
2010 Gallic acid induces G2/M phase cell cycle arrest via regulating 14-3-3β release from Cdc25C and Chk2 activation in human bladder transitional carcinoma cells. Molecular nutrition & food research 35 20564478
2014 Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2 production in keratinocyte is related to reactive oxygen species, CYP1A1, Src, EGFR and Ras signaling. PloS one 33 25051199
2006 Checkpoint kinase 1-mediated phosphorylation of Cdc25C and bad proteins are involved in antitumor effects of loratadine-induced G2/M phase cell-cycle arrest and apoptosis. Molecular carcinogenesis 33 16649252
2019 CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death. Molecular carcinogenesis 32 31237025
2014 Cantharidin induces G2/M phase arrest by inhibition of Cdc25c and Cyclin A and triggers apoptosis through reactive oxygen species and the mitochondria‑dependent pathways of A375.S2 human melanoma cells. International journal of oncology 31 25340978
2010 Survivin mediates self-protection through ROS/cdc25c/CDK1 signaling pathway during tumor cell apoptosis induced by high fluence low-power laser irradiation. Cancer letters 31 20579806
2006 The dual specificity phosphatase Cdc25C is a direct target for transcriptional repression by the tumor suppressor p53. Cell cycle (Georgetown, Tex.) 31 16582636
2000 Selective requirement for Cdc25C protein synthesis during meiotic progression in porcine oocytes. Biology of reproduction 31 10684791
2018 Proteasome mediated degradation of CDC25C and Cyclin B1 in Demethoxycurcumin treated human glioma U87 MG cells to trigger G2/M cell cycle arrest. Toxicology and applied pharmacology 30 30009775
2018 Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 30 30537743
2010 Cyclin E deregulation impairs mitotic progression through premature activation of Cdc25C. Cancer research 30 20530684
2008 Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosis. Cell cycle (Georgetown, Tex.) 30 18604163
2005 Changes in regulatory phosphorylation of Cdc25C Ser287 and Wee1 Ser549 during normal cell cycle progression and checkpoint arrests. Molecular biology of the cell 30 16195348

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