Affinage

CDC25C

M-phase inducer phosphatase 3 · UniProt P30307

Length
473 aa
Mass
53.4 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDC25C is a dual-specificity phosphatase that dephosphorylates and activates the CDK1(Cdc2)/cyclin B complex to trigger mitotic entry, functioning as a central integrator of cell cycle and checkpoint signals at the G2/M transition (PMID:1828290, PMID:1655274). Its phosphatase activity is amplified by a positive feedback loop in which CDK1/cyclin B phosphorylates CDC25C, and is further stimulated by Polo-like kinase (Plk1)-dependent phosphorylation that promotes nuclear translocation, by ERK-mediated phosphorylation, and by CaM kinase II (PMID:8428594, PMID:8703070, PMID:11897663, PMID:17382881). Checkpoint kinases Chk1 and Chk2 phosphorylate Ser-216, creating a 14-3-3 binding site that enforces cytoplasmic sequestration and prevents mitotic entry in response to DNA damage or replication stress, while PP2A (particularly the B56δ subunit) opposes activating phosphorylations during interphase and at mitotic exit, with Pin1 prolyl isomerase facilitating PP2A-mediated dephosphorylation of specific pSer-Pro motifs (PMID:9278512, PMID:9889122, PMID:8389619, PMID:18056802, PMID:11090625). Despite its central biochemical role, CDC25C is dispensable in mice due to functional compensation by CDC25A and CDC25B (PMID:11359894).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1991 High

    Establishing CDC25C as a catalytically active phosphatase answered the question of whether CDC25 family members possess intrinsic enzymatic activity and identified the active-site cysteine as essential, defining the protein as a dual-specificity phosphatase that directly dephosphorylates and activates CDK1/cyclin B.

    Evidence In vitro phosphatase assays with site-directed mutagenesis of the catalytic cysteine; reconstitution with purified CDK1/cyclin B and H1 kinase readout

    PMID:1655274 PMID:1828290

    Open questions at the time
    • Crystal structure of CDC25C catalytic domain not yet solved in this work
    • Substrate specificity relative to CDC25A/B not established
  2. 1992 High

    Demonstrating that CDC25C activity oscillates with the cell cycle and is negatively regulated by PP2A/PP1 established that reversible phosphorylation controls CDC25C activation state, with PP2A maintaining the low-activity interphase form.

    Evidence Xenopus egg extracts with okadaic acid treatment and in vitro dephosphorylation by PP1/PP2A; gel-mobility shift and kinase activity assays

    PMID:1392080 PMID:8389619

    Open questions at the time
    • Specific PP2A holoenzyme subunit identity not determined
    • Whether PP2A acts directly on CDC25C or through an intermediary not resolved
  3. 1993 High

    Identifying CDK1/cyclin B as both a substrate and an activating kinase for CDC25C established the positive feedback loop underlying MPF autoamplification at mitotic entry.

    Evidence In vitro phosphorylation by Cdc2/cyclin B increasing CDC25C phosphatase activity; thiophosphate-stabilized CDC25C triggering oocyte maturation in Xenopus extracts

    PMID:8428594

    Open questions at the time
    • Identity and stoichiometry of activating phosphorylation sites on CDC25C not mapped
    • Whether cyclin A-CDK complexes contribute was excluded but mechanism of exclusion not detailed
  4. 1994 High

    Purification of an interphase Ser-216 kinase and mapping of the kinase-binding region (aa 200–256) established that a dedicated kinase phosphorylates the key inhibitory site, preceding the later identification of this activity as Chk1/Chk2.

    Evidence Biochemical purification from rat liver (~8000-fold); in vitro kinase assay; deletion mapping

    PMID:7982962

    Open questions at the time
    • Molecular identity of the purified kinase not determined in this study
  5. 1996 High

    Identification of Polo-like kinase (Plx1) as a direct activating kinase for CDC25C revealed a second input—besides CDK1 itself—that drives CDC25C phosphorylation and activation at mitotic entry.

    Evidence Purification of Plx1 from Xenopus egg extracts; in vitro phosphorylation of CDC25C N-terminus increasing phosphatase activity; MPM-2 reactivity

    PMID:8703070

    Open questions at the time
    • Specific phosphorylation sites on CDC25C not mapped
    • Whether Plx1 is essential for CDC25C activation in mammalian cells not tested
  6. 1997 High

    Discovery that Chk1 phosphorylates CDC25C on Ser-216 to create a 14-3-3 binding site established the molecular basis of the DNA damage G2 checkpoint, explaining how checkpoint signaling blocks mitotic entry by sequestering CDC25C.

    Evidence In vitro Chk1 kinase assay; 14-3-3 binding with S216A mutagenesis abolishing binding; checkpoint override with S216A mutant; genetic epistasis in fission yeast

    PMID:9278510 PMID:9278511 PMID:9278512

    Open questions at the time
    • Relative contributions of Chk1 vs other Ser-216 kinases in unperturbed cells unknown
    • Whether 14-3-3 binding actively exports CDC25C or blocks import not resolved
  7. 1999 High

    Chk2/Cds1 was shown to converge on the same inhibitory phosphorylation sites as Chk1, and 14-3-3 binding was demonstrated to enforce nuclear exclusion of Cdc25, unifying the replication and DNA damage checkpoint mechanisms through cytoplasmic sequestration.

    Evidence In vitro Chk2 kinase assay with ATM-dependent cellular validation; fission yeast 14-3-3 binding mutant with leptomycin B and localization microscopy; Cds1 phosphorylation site mapping

    PMID:10198041 PMID:10523629 PMID:9774107 PMID:9889122

    Open questions at the time
    • Quantitative contribution of each checkpoint kinase to Ser-216 phosphorylation in human cells not determined
  8. 1999 High

    Demonstration that CaM kinase II and Polo-like kinase (Plx1) are each individually required for CDC25C activation expanded the activating kinase network beyond the CDK1 feedback loop, with Plx1 immunodepletion completely blocking CDC25C activation.

    Evidence In vitro CaM kinase II phosphorylation increasing CDC25C activity plus KN-93 inhibitor blocking G2/M in HeLa cells; Plx1 immunodepletion from Xenopus extracts preventing CDC25C and Cdc2 activation

    PMID:10075693 PMID:11408585

    Open questions at the time
    • CaM kinase II phosphorylation sites on CDC25C not mapped
    • Whether Plx1 requirement is conserved in mammalian somatic cells not tested
  9. 2000 High

    Pin1 prolyl isomerase was shown to catalyze cis-to-trans isomerization of phospho-Ser/Thr-Pro motifs in CDC25C, rendering them substrates for the trans-specific phosphatase PP2A—establishing conformational regulation as a mechanism coupling phosphorylation to dephosphorylation.

    Evidence In vitro prolyl isomerization and PP2A dephosphorylation assays demonstrating conformation specificity; genetic interactions in yeast; isomerase-dead mutant

    PMID:11090625

    Open questions at the time
    • Which specific pSer-Pro sites on CDC25C are Pin1/PP2A targets not fully mapped
    • In vivo validation of this mechanism in mammalian cells limited
  10. 2001 High

    Dissection of CDC25C nuclear-cytoplasmic trafficking revealed that 14-3-3 binding inhibits nuclear import rather than promoting export, and that an intrinsic NES cooperates with 14-3-3 binding to maintain cytoplasmic localization; meanwhile, genetic knockout showed CDC25C is dispensable in mice.

    Evidence Leptomycin B treatment, NES mutation, S216A mutation with GFP-CDC25C live imaging; Cdc25C knockout mice with normal viability, fertility, and checkpoint responses

    PMID:11313932 PMID:11359894

    Open questions at the time
    • Mechanism of functional compensation by CDC25A/B not characterized
    • Whether triple CDC25 knockout is lethal not tested
  11. 2002 High

    Multiple regulatory inputs on CDC25C were mapped: Plk1 phosphorylation of Ser-198 within the NES promotes nuclear accumulation at prophase; PKA phosphorylation of Ser-287 enforces G2 arrest via 14-3-3; and oxidative stress induces an intramolecular disulfide bond triggering 14-3-3 binding and proteasomal degradation.

    Evidence Plk1 kinase assay with S198A mutant localization; PKA phosphorylation with S287A bypass of G2 arrest in Xenopus oocytes; H2O2-induced disulfide bond detection with Cys mutagenesis and stability measurements

    PMID:11897663 PMID:11925443 PMID:12477927

    Open questions at the time
    • Whether Plk1-Ser198 phosphorylation disrupts CRM1/NES interaction not shown directly
    • Physiological relevance of oxidative disulfide regulation in vivo not established
  12. 2003 High

    Discovery that mitotic Ser-214 phosphorylation blocks adjacent Ser-216 phosphorylation and 14-3-3 binding provided a molecular switch explaining how CDC25C escapes checkpoint inhibition during mitotic entry, while JNK-mediated Ser-168 phosphorylation was identified as a stress-induced inhibitory modification.

    Evidence S214A mutagenesis restoring Ser-216 phosphorylation and 14-3-3 binding during mitosis with delayed entry; JNK kinase assay with S168A mutant reversing stress-induced CDC25C inhibition

    PMID:12742231 PMID:12766774

    Open questions at the time
    • Kinase responsible for Ser-214 phosphorylation not identified
    • Relationship between JNK and Chk1 pathways at CDC25C not clarified
  13. 2005 Medium

    Additional regulatory kinases were identified: Pim-1 phosphorylates and activates CDC25C to promote G2/M progression, and the stress-activated kinase Srk1 (p38/Sty1 pathway) phosphorylates the same sites as Chk1/Cds1 to delay mitosis during stress in fission yeast.

    Evidence In vitro Pim-1 kinase assay with co-IP and cell cycle analysis; Srk1 kinase assay with 14-3-3 binding and localization in fission yeast

    PMID:15629716 PMID:16356754

    Open questions at the time
    • Pim-1 phosphorylation sites on CDC25C not mapped
    • Whether Srk1-like pathway (MK2) acts on human CDC25C not tested
  14. 2007 High

    ERK was identified as a direct mitotic kinase for CDC25C at T48 (and additional Xenopus sites), while PP2A-B56δ was established as the specific phosphatase holoenzyme that dephosphorylates CDC25C at mitotic exit; LZTS1 was shown to stabilize the CDK1-CDC25C interaction during mitosis.

    Evidence ERK purification from M-phase extracts with site mapping and MEK inhibitor effects on mitotic entry; B56δ knockdown/knockout showing prolonged CDC25C hyperphosphorylation and delayed mitotic exit; Lzts1 knockout MEFs with accelerated CDC25C degradation and reduced CDK1 activity

    PMID:17349584 PMID:17382881 PMID:18056802

    Open questions at the time
    • Whether ERK acts catalytically or as a scaffold for CDC25C activation not distinguished
    • Direct physical interaction between B56δ-PP2A and CDC25C not demonstrated by reconstitution
  15. 2008 High

    Greatwall kinase was positioned upstream of CDC25C activation by showing it promotes CDC25C phosphorylation through inhibition of an opposing phosphatase (later identified as PP2A-B55), independent of CDK1, Plx1, or MAPK.

    Evidence Xenopus egg extracts with Greatwall immunodepletion and add-back; comparison with okadaic acid effects; CDC25C phosphorylation assay

    PMID:18199678

    Open questions at the time
    • Direct substrate of Greatwall (later shown to be ENSA/Arpp19 inhibiting PP2A-B55) not identified in this study
    • Whether Greatwall acts on CDC25C through PP2A-B55 vs B56 not distinguished
  16. 2023 Medium

    PUF60-dependent exon 3 inclusion was identified as essential for CDC25C mRNA stability via NMD suppression, revealing a post-transcriptional layer of CDC25C regulation that impacts G2/M progression.

    Evidence siRNA knockdown of PUF60; RNA-seq and RT-PCR showing exon 3 skipping; CDC25C protein loss; cell cycle arrest; xenograft assay

    PMID:37682709

    Open questions at the time
    • Whether PUF60-dependent splicing is cell cycle regulated not shown
    • Whether this mechanism is relevant in non-cancer cell types not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for how multi-site phosphorylation collectively modulates CDC25C conformation and activity, the precise mechanism by which CDC25A/B compensate for CDC25C loss in vivo, and how the numerous kinase inputs are temporally coordinated to produce a switch-like activation at mitotic entry.
  • No high-resolution structure of full-length CDC25C with regulatory phosphorylations
  • Quantitative modeling of the multi-kinase/phosphatase network controlling CDC25C lacking
  • Mechanism of functional redundancy among CDC25 family members uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4
Pathway
R-HSA-1640170 Cell Cycle 8 R-HSA-73894 DNA Repair 5
Partners
CCNB1CDK1CHEK1CHEK2PIN1PLK1YWHABYWHAE

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CDC25C possesses intrinsic dual-specificity phosphatase activity; the active-site cysteine residue is essential for catalysis, as shown by NEM treatment and site-directed mutagenesis abolishing activity. In vitro phosphatase assays with model substrates (pNPP, phosphotyrosine peptides), site-directed mutagenesis of conserved cysteine, chemical inhibition with NEM and vanadate Cell High 1655274
1991 Human CDC25C (p54CDC25H) directly dephosphorylates and activates the p34cdc2/cyclin B complex, triggering H1 histone kinase activity. In vitro reconstitution: purified bacterial GST-CDC25H added to purified inactive starfish p34cdc2/cyclin B complex; H1 kinase assay Nature High 1828290
1992 CDC25C (cdc25Hs) is itself a phosphatase that directly dephosphorylates p34cdc2 on tyrosine; the catalytic domain resides in the C-terminus. GST-fusion protein overproduction in bacteria, Xenopus oocyte maturation assay, immune-complex kinase assay, pNPP phosphatase assay, deletion analysis Molecular biology of the cell High 1312880
1993 CDC25C phosphatase activity is directly activated by phosphorylation during mitosis; Cdc2-cyclin B phosphorylates and activates CDC25C, forming a positive feedback loop for MPF self-amplification. CDC25C is not a substrate of cyclin A-associated kinases. In vitro phosphorylation by cdc2-cyclin B and mitotic HeLa extracts; phosphatase activity assay; stable thiophosphorylation required for CDC25C to activate cdc2-cyclin B1 in Xenopus egg extracts and induce oocyte maturation The EMBO journal High 8428594
1992 CDC25 (Xenopus ortholog) phosphatase activity oscillates during the cell cycle, peaking at M phase coincident with hyperphosphorylation of its N-terminal region; dephosphorylation by PP1 or PP2A reduces its activity back to interphase levels. Xenopus egg/oocyte extracts; okadaic acid treatment; in vitro dephosphorylation; gel-mobility shift assays; cyclin B/cdc2 kinase activity assay Molecular biology of the cell High 1392080
1993 PP2A (type-2A protein phosphatase) negatively regulates CDC25C by keeping it dephosphorylated and in a low-activity state during interphase; PP2A maintains CDC25C inactive as part of the mechanism by which unreplicated DNA prevents mitotic entry. Xenopus egg extracts; okadaic acid and inhibitor-2 (PP1-specific) treatment; addition of purified PP2A catalytic subunit; CDC25C dephosphorylation assay Molecular biology of the cell High 8389619
1996 Plx1 (Xenopus Polo-like kinase) physically associates with and phosphorylates the N-terminal domain of CDC25, stimulating its phosphatase activity; Plx1-phosphorylated CDC25 reacts with the mitotic phosphoprotein antibody MPM-2. Purification from Xenopus egg extracts; cDNA cloning; recombinant Plx1 phosphorylation of CDC25 in vitro; phosphatase activity assay; MPM-2 immunoreactivity Science (New York, N.Y.) High 8703070
1997 Chk1 kinase phosphorylates CDC25C on serine-216 in vitro and in vivo; this phosphorylation creates a binding site for 14-3-3 proteins, which negatively regulate CDC25C, preventing activation of Cdc2-cyclin B and mitotic entry in response to DNA damage. In vitro kinase assay (Chk1 phosphorylation of CDC25C); phosphospecific analysis; 14-3-3 binding assay; S216A mutation abrogating 14-3-3 binding; conditional overexpression of S216A mutant; G2 checkpoint assay (unreplicated DNA, irradiation) Science (New York, N.Y.) High 9278511 9278512
1997 In fission yeast, Cdc25 (but not Wee1) is the primary target of the DNA damage checkpoint kinase Chk1; Cdc25 associates with Chk1 in vivo and is phosphorylated in Chk1 complexes. Genetic epistasis (cdc2-3w Δcdc25 fission yeast); Chk1 overexpression; co-immunoprecipitation and kinase assay of Chk1-Cdc25 complex Science (New York, N.Y.) High 9278510
1998 In fission yeast, both Chk1 and Cds1 checkpoint kinases phosphorylate Cdc25 on the same sites (Ser-99, Ser-192, Ser-359); this promotes 14-3-3 binding and is required for the replication checkpoint. In vitro kinase assay (Chk1 and Cds1 phosphorylation of Cdc25); alanine substitution mutagenesis; 14-3-3 binding assay in vitro; checkpoint assay in vivo Nature High 9774107
1999 Human Chk2 (Cds1 homolog) directly phosphorylates and inactivates CDC25C in vitro; Cds1/Chk2 is activated by DNA damage and decreases CDC25C activity in irradiated cells, dependent on ATM. In vitro kinase assay; CDC25C phosphatase activity assay after irradiation; wortmannin inhibition; ATM-dependence analysis Current biology : CB High 9889122
1994 A serine kinase that associates with and phosphorylates CDC25C on serine-216 was purified (~36–38 kDa doublet from rat liver); the kinase binds CDC25C within amino acids 200–256. Biochemical purification (8000-fold) from rat liver; in vitro kinase assay; deletion mapping of binding domain The Journal of biological chemistry High 7982962
1995 14-3-3 proteins (epsilon and beta isoforms) physically interact with CDC25A and CDC25B (and by extension CDC25C family) both in vitro and in vivo; 14-3-3 binding does not directly affect CDC25A phosphatase activity but may facilitate CDC25-Raf-1 association. Yeast two-hybrid screen; in vitro and in vivo co-immunoprecipitation; phosphatase activity assay Proceedings of the National Academy of Sciences of the United States of America Medium 7644510
1999 In fission yeast, 14-3-3 binding to Cdc25 is required for nuclear exclusion of Cdc25 and for both DNA damage and replication checkpoints; overproduction of Rad24 (14-3-3) causes nuclear exclusion of wild-type but not 14-3-3 binding mutant Cdc25. 14-3-3 binding mutant generation; leptomycin B (nuclear export inhibition); subcellular localization by microscopy; checkpoint assay in fission yeast Molecular and cellular biology High 10523629
2000 Pin1 catalyzes cis-trans prolyl isomerization of phospho-Ser/Thr-Pro motifs in CDC25C, facilitating dephosphorylation by PP2A, which is conformation-specific (acts only on trans isomer); Pin1 and PP2A show reciprocal genetic interactions and Pin1 prolyl isomerase activity is essential for cell division. In vitro prolyl isomerization and dephosphorylation assays; PP2A conformation-specificity assay; genetic interaction in yeast; Pin1 isomerase-dead mutant Molecular cell High 11090625
2001 CDC25C localization is regulated by both an intrinsic nuclear export signal (NES) in the N-terminus and 14-3-3 binding; 14-3-3 binding does not drive nuclear export but negatively regulates nuclear import; complete nuclear accumulation requires loss of both NES function and 14-3-3 binding. Leptomycin B treatment; NES mutation; S216A mutation (14-3-3 binding-deficient); GFP-CDC25C live imaging and immunofluorescence Oncogene High 11313932
2002 Plk1 phosphorylates CDC25C on Ser198 within its nuclear export signal during prophase, promoting nuclear translocation of CDC25C; S198A mutant CDC25C remains cytoplasmic when wild-type CDC25C accumulates in the nucleus. Kinase assay; phospho-specific antibody; GFP-CDC25C live-cell imaging; constitutively active Plk1 overexpression; S198A mutant phenotype EMBO reports High 11897663
2002 G2 arrest of Xenopus oocytes by PKA is mediated through phosphorylation of CDC25 on Ser-287, causing 14-3-3 sequestration; progesterone-induced oocyte maturation involves dephosphorylation of Ser-287 just before Cdc2 dephosphorylation; S287A mutant bypasses PKA-mediated G2 arrest. In vitro PKA phosphorylation assay; 14-3-3 binding assay; phospho-Ser-287 antibody; PKI overexpression; S287A mutant microinjection; oocyte maturation assay Proceedings of the National Academy of Sciences of the United States of America High 12477927
2002 Oxidative stress (H2O2) induces an intramolecular disulfide bond between the CDC25C active-site Cys377 and Cys330; this bond promotes 14-3-3 binding and triggers proteasome-dependent degradation of CDC25C independently of Chk1. In vitro H2O2 treatment; disulfide bond detection; Cys-to-Ser mutagenesis (C330S, C377S, double C2 mutant); 14-3-3 binding assay; stability measurement The Journal of biological chemistry High 11925443
2003 CDC25C phosphorylation on Ser-214 during mitosis prevents phosphorylation of the adjacent inhibitory Ser-216 site, thus preventing 14-3-3 binding; S214A mutation reconstitutes Ser-216 phosphorylation and 14-3-3 binding during mitosis and delays mitotic entry. Phospho-specific antibodies; S214A and S216A mutagenesis; 14-3-3 binding assay; HeLa cell depletion/reconstitution with mutant CDC25C; time-to-mitosis assay Nature cell biology High 12766774
2004 p53 directly represses CDC25C transcription by binding to a specific site in the cdc25C promoter; a second mechanism involves the CDE/CHR repressor element; both mechanisms contribute to p53-dependent G2 arrest following DNA damage. Chromatin immunoprecipitation (ChIP); promoter reporter assays; mutational analysis of p53-binding site and CDE/CHR elements; comparison at physiologically relevant p53 levels induced by DNA damage Molecular cell High 15574328
1999 Polo-like kinase Plx1 is required for activation of CDC25C in Xenopus cell-free extracts; immunodepletion of Plx1 completely prevents CDC25C activation and cyclin B-Cdc2 activation; CDC25C activation maintenance during mitosis does not require cyclin B-Cdc2 activity. Immunodepletion of Plx1 from Xenopus oocyte extract; PKI-stimulated maturation assay; p21Cip1 inhibition of cyclin B-Cdc2; kinase activity assays Molecular biology of the cell High 11408585
1999 In fission yeast, Cds1 inhibits Cdc25 in vitro and in vivo, contributing to the replication checkpoint; both Cds1 and Chk1 phosphorylate Cdc25 predominantly on Ser-99; Cdc25-S99A partially impairs replication and damage checkpoints in vivo. In vitro kinase assay; in vivo checkpoint assay; alanine mutagenesis of phosphorylation sites; CDC25 phosphatase-dependent mitosis rate assay Molecular biology of the cell High 10198041
1999 CaM kinase II phosphorylates CDC25C in vitro and increases its phosphatase activity ~2.5–3-fold; inhibition of CaM kinase II in HeLa cells blocks G2/M entry with CDC25C remaining unphosphorylated and Cdc2 remaining tyrosine-phosphorylated. In vitro CaM kinase II phosphorylation assay; CDC25C phosphatase activity assay; KN-93 inhibitor treatment; microinjection of AC3-I peptide inhibitor; cell cycle analysis; Cdc2 tyrosine phosphorylation and H1 kinase assay The Journal of biological chemistry Medium 10075693
2001 CDC25C is dispensable for normal mitosis, meiosis, and the DNA damage checkpoint response in mice; Cdc25C-/- mice are viable and fertile, and Cdc25C-/- MEFs show normal Cdc2 phosphorylation and mitotic timing, suggesting compensation by Cdc25A and/or Cdc25B. Cdc25C knockout mouse generation; developmental and fertility analysis; T/B cell development; MEF cell cycle analysis; Cdc2 phosphorylation and DNA damage response assay Molecular and cellular biology High 11359894
1999 Prk (Plk3) physically interacts with CDC25C and directly phosphorylates it on Ser-216 in vitro; co-infection with Prk enhances CDC25C kinase activity in insect cells. Baculoviral co-expression; in vitro kinase assay; co-immunoprecipitation; affinity column chromatography; phosphopeptide mapping Oncogene Medium 10557092
2002 Arsenite induces CDC25C degradation via the ubiquitin-proteasome pathway; a KEN-box motif (residues 151–157) is required for arsenite-induced ubiquitination of CDC25C. Cell cycle analysis; KEN-box mutagenesis; peptide competitor assay; ubiquitination assay Proceedings of the National Academy of Sciences of the United States of America Medium 11842186
2005 Pim-1 kinase directly interacts with CDC25C and phosphorylates its N-terminal region, enhancing CDC25C phosphatase activity; Pim-1 and CDC25C co-localize in the cytoplasm; Pim-1 expression enhances G2/M progression in bleomycin-arrested cells. In vitro kinase assay; co-immunoprecipitation; immunofluorescence co-localization; CDC25C phosphatase activity assay; cell cycle analysis in transfected cells The international journal of biochemistry & cell biology Medium 16356754
2007 ERK/MAPK (p42 MAPK/ERK2) directly phosphorylates CDC25 at T48, T138, and S205 in Xenopus and phosphorylates human CDC25C at T48 in mitosis; ERK interacts with CDC25C in interphase; ERK inhibition partially reduces T48 phosphorylation, CDC25C activation, and mitotic entry. Biochemical fractionation and kinase identification in Xenopus M-phase extracts; phosphorylation site mapping; kinase assay; co-immunoprecipitation in mammalian cells; MEK inhibitor (U0126) treatment; mitotic entry assay Cell High 17382881
2003 SAPK/JNK directly phosphorylates CDC25C on Ser-168 in vitro; stress-induced Ser-168 phosphorylation in vivo correlates with loss of CDC25C phosphatase activity and inhibition of Cdc2/cyclin B; S168A mutant reverses stress-induced Cdc2/cyclin B inhibition. In vitro kinase assay; phospho-specific antibody (pS168); CDC25C phosphatase activity assay; S168A mutagenesis; Cdc2/cyclin B kinase assay Cellular signalling Medium 12742231
2007 PP2A:B56delta regulates CDC25C at mitosis; failure of PP2A:B56delta to dephosphorylate CDC25C leads to prolonged hyperphosphorylation and activation of CDC25C, persistent Cdk1 activation, and delayed mitotic exit; stable knockdown of B56delta leads to compensatory upregulation of Wee1. B56delta knockdown (siRNA and stable); mouse knockout; CDC25C phosphorylation and activity assay; Cdk1 activity assay; mitotic exit timing; Wee1 expression analysis Proceedings of the National Academy of Sciences of the United States of America High 18056802
2007 LZTS1 (Fez1) protein is required for proper Cdk1/Cdc25C interaction; in Lzts1-/- MEFs, CDC25C is more rapidly degraded during M phase, resulting in decreased Cdk1 activity, accelerated mitotic progression, and improper chromosome segregation. Lzts1 knockout mouse and MEFs; co-immunoprecipitation of Cdk1/Cdc25C; CDC25C protein stability measurement; Cdk1 activity assay; mitotic timing; taxol/nocodazole response Cancer cell High 17349584
2005 In fission yeast, the stress-activated kinase Srk1 (downstream of p38/Sty1 MAPK) directly phosphorylates Cdc25 at the same sites as Chk1 and Cds1, inducing 14-3-3 (Rad24) binding and cytoplasmic accumulation of Cdc25 to delay mitotic entry during stress. In vitro kinase assay; co-immunoprecipitation; localization; cell cycle delay assay; srk1 knockout and overexpression phenotypes Molecular cell High 15629716
2008 Greatwall kinase promotes CDC25 activation and M-phase entry in Xenopus by negatively regulating a phosphatase that inhibits Cdc25; activated Greatwall drives Cdc25 phosphorylation independently of Cdc2, Plx1, or MAPK activity, mimicking okadaic acid (PP2A inhibitor) effects. Xenopus egg extracts; immunodepletion; activated Greatwall addition; PKA activator to block maturation; CDC25 phosphorylation assay; meiotic maturation assay Molecular biology of the cell High 18199678
1992 CDC25C (cdc25) protein is constitutively expressed throughout the mammalian cell cycle and is localized predominantly in the nucleus during interphase and early prophase; it redistributes throughout the cytoplasm at the prophase-prometaphase boundary. Immunofluorescence with affinity-purified antibodies; Western blot across cell cycle stages The Journal of cell biology Medium 1500423
1992 Hamster CDC25C localizes predominantly to the cytoplasm (periphery of nuclei) in hydroxyurea-arrested cells and translocates to the nucleus upon loss of RCC1 function; anti-CDC25C antibody microinjection blocks chromosome condensation induced by RCC1 loss, indicating CDC25C is required for Cdc2 activation under these conditions. cDNA cloning; antibody microinjection; immunofluorescence localization; chromosome condensation assay; gel mobility shift Molecular biology of the cell Medium 1337289
2023 PUF60 splicing factor promotes mitotic CDC25C expression by preventing exon 3 skipping; PUF60 depletion causes exon 3 skipping leading to nonsense-mediated mRNA decay and CDC25C protein loss, impairing G2/M transition. siRNA knockdown; RNA-seq; RT-PCR of alternative splicing; Western blot for CDC25C; cell cycle analysis; tumor xenograft assay 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.) 1191 9278512
1997 Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science (New York, N.Y.) 1134 9278511
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
1991 The cdc25 protein contains an intrinsic phosphatase activity. Cell 548 1655274
1991 Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein. Nature 535 1828290
1996 Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. Science (New York, N.Y.) 484 8703070
1997 Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase. Science (New York, N.Y.) 482 9278510
2000 Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins. Molecular cell 474 11090625
1987 The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. Cell 432 3545497
1992 Regulation of the cdc25 protein during the cell cycle in Xenopus extracts. Cell 365 1623517
2003 Regulating mammalian checkpoints through Cdc25 inactivation. EMBO reports 346 12835754
2006 The when and wheres of CDC25 phosphatases. Current opinion in cell biology 328 16488126
2000 Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25C. Current opinion in cell biology 317 11063929
2000 Cell cycle regulation by the Cdc25 phosphatase family. Progress in cell cycle research 314 10740819
1998 Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1. Nature 314 9774107
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
1992 Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity. Molecular biology of the cell 258 1392080
2002 The rhodanese/Cdc25 phosphatase superfamily. Sequence-structure-function relations. EMBO reports 255 12151332
1999 A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. Current biology : CB 240 9889122
1995 14-3-3 proteins associate with cdc25 phosphatases. Proceedings of the National Academy of Sciences of the United States of America 240 7644510
2020 The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review. Cancer cell international 229 32518522
2006 Cdc25: mechanisms of checkpoint inhibition and recovery. Trends in cell biology 216 16682204
1992 cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2. Molecular biology of the cell 196 1312880
2002 Redox regulation of Cdc25C. The Journal of biological chemistry 187 11925443
1986 Characterization, cloning and sequence analysis of the CDC25 gene which controls the cyclic AMP level of Saccharomyces cerevisiae. The EMBO journal 186 3011405
2002 G2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A. Proceedings of the National Academy of Sciences of the United States of America 179 12477927
1999 Cdc25 inhibited in vivo and in vitro by checkpoint kinases Cds1 and Chk1. Molecular biology of the cell 176 10198041
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
2002 Dual mode of degradation of Cdc25 A phosphatase. The EMBO journal 168 12234927
1991 The CDC25 protein of Saccharomyces cerevisiae promotes exchange of guanine nucleotides bound to ras. Molecular and cellular biology 167 2017169
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