Affinage

CDC5L

Cell division cycle 5-like protein · UniProt Q99459

Length
802 aa
Mass
92.3 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDC5L is a core subunit of the Prp19/CDC5L spliceosomal complex that is essential for catalytic activation of the spliceosome, particularly the second transesterification step of pre-mRNA splicing (PMID:11101529, PMID:10570151). The stable Prp19/CDC5L core comprises CDC5L, hPrp19, PRL1, and SPF27 in an elongated asymmetric architecture, with CDC5L additionally engaging PLRG1 through its C-terminal domain and the PLRG1 WD40 repeat, an interaction required for splicing catalysis (PMID:20176811, PMID:11544257, PMID:14576297). CDC5L splicing activity is regulated by CDK2-mediated phosphorylation at T411/T438, and CDC5L interacts with hnRNP-M to modulate alternative splicing and directly binds target pre-mRNAs through its N-terminal Myb-like domain to influence transcript-specific splicing outcomes (PMID:18583928, PMID:20467437, PMID:34298017, PMID:25263959). Beyond splicing, CDC5L physically interacts with the checkpoint kinase ATR and is required for ATR-dependent S-phase checkpoint signaling, and its depletion causes mitotic catastrophe with chromosome misalignment and sustained spindle assembly checkpoint activation (PMID:19633697, PMID:24675469).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 Medium

    The initial question of whether CDC5L has a cell-cycle function was answered by showing that its overexpression accelerates G2/M progression and a dominant-negative mutant delays mitotic entry, establishing CDC5L as a positive regulator of G2-M transition.

    Evidence Overexpression and dominant-negative mutant analysis in mammalian cells with cell cycle profiling

    PMID:9468527

    Open questions at the time
    • Mechanism linking CDC5L to G2/M control was not identified
    • Relationship to splicing function was unknown
  2. 1999 High

    The fundamental question of whether CDC5L functions in pre-mRNA splicing was resolved by demonstrating that mammalian CDC5 associates with core splicing machinery and spliceosomal complexes, and that the yeast homolog CEF1 is required for the first splicing step.

    Evidence Co-immunoprecipitation from nuclear extracts, in vitro spliceosome association, yeast CEF1 depletion

    PMID:10570151

    Open questions at the time
    • Which catalytic step CDC5L promotes was not resolved for the human protein
    • Complex composition was unknown
  3. 2000 High

    Two advances defined CDC5L's biochemical framework: its immunodepletion from HeLa nuclear extract specifically blocked the second catalytic step of splicing, and its phosphorylation by cyclin E-Cdk2 was shown to mediate interaction with the FHA domain of NIPP1-PP1, linking splicing regulation to cell-cycle kinase signaling.

    Evidence Immunodepletion/add-back in vitro splicing assay; yeast two-hybrid, co-IP, and FHA domain mutagenesis for NIPP1 interaction

    PMID:10827081 PMID:11101529

    Open questions at the time
    • Specific phosphorylation sites on CDC5L were not mapped
    • Structural basis of complex assembly unknown
  4. 2000 Medium

    CDC5L was shown to bind a specific 12 bp DNA sequence through its amino terminus and activate transcription in a reporter assay, raising the possibility of a DNA-binding activity separate from its splicing role.

    Evidence In vitro DNA binding assay and transcription reporter in yeast

    PMID:11082045

    Open questions at the time
    • No endogenous transcriptional targets identified
    • Relevance of DNA binding to CDC5L's primary splicing function unclear
  5. 2001 High

    The direct interaction between CDC5L and PLRG1 was mapped to the CDC5L C-terminal domain and PLRG1 WD40 repeats, and disrupting this interaction inhibited splicing, establishing this partnership as functionally essential.

    Evidence Co-IP, in vitro binding, domain mapping, and competitive inhibition of in vitro splicing

    PMID:11544257 PMID:14576297

    Open questions at the time
    • Structural details of the CDC5L-PLRG1 interface unknown
    • Whether PLRG1 is part of the stable Prp19/CDC5L core was unresolved
  6. 2008 High

    The question of how cell-cycle kinases regulate CDC5L's splicing function was answered by identifying CDK2-dependent phosphorylation at T411 and T438 as required for splicing activity, directly coupling CDC5L catalytic competence to cell-cycle status.

    Evidence 2D phosphopeptide mapping, mass spectrometry, site-directed mutagenesis, CDK2 inhibitor treatment, in vitro splicing

    PMID:18583928

    Open questions at the time
    • Whether phosphorylation affects specific protein-protein interactions within the Prp19 complex was not tested
    • In vivo splicing consequences of phospho-mutants not examined
  7. 2009 High

    CDC5L was discovered to function in the DNA damage response by physically interacting with ATR and being required for ATR-mediated checkpoint signaling, expanding its role beyond splicing.

    Evidence Co-IP, RNAi knockdown, checkpoint activation assays for Chk1/Rad17/FancD2, deletion mutant rescue

    PMID:19633697

    Open questions at the time
    • Whether ATR interaction is independent of splicing function was not resolved
    • Structural basis of CDC5L-ATR interaction unknown
  8. 2010 High

    The architecture of the Prp19/CDC5L complex was defined: a stable core of CDC5L, hPrp19 (4 copies), PRL1, and SPF27 adopts an elongated ~20 nm structure, and hnRNP-M was identified as a CDC5L/PLRG1 interactor required for alternative splicing regulation.

    Evidence Native complex purification, stoichiometry analysis, EM, limited proteolysis; co-IP with hnRNP-M domain mutant and alternative splicing reporter

    PMID:20176811 PMID:20467437

    Open questions at the time
    • High-resolution structure of the intact complex was lacking
    • How hnRNP-M modulates splice site selection through CDC5L unknown
  9. 2011 Medium

    CTNNBL1 was shown to bind the NLS region of CDC5L via its armadillo domain, explaining how CTNNBL1 associates with the Prp19 complex through a non-canonical import-like interaction.

    Evidence Co-IP, domain mapping, NLS peptide binding assays

    PMID:21385873

    Open questions at the time
    • Functional consequence of disrupting CTNNBL1-CDC5L interaction on splicing not tested in this study
    • Whether CTNNBL1 truly acts as an import factor or intranuclear chaperone was ambiguous
  10. 2014 Medium

    Two studies clarified distinct aspects of CDC5L biology: its N-terminal Myb-like domain was shown to bind RNA (including dsRNA) in fission yeast, and CDC5L depletion in human cells caused mitotic catastrophe with chromosome misalignment and checkpoint activation traceable to mis-splicing of mitotic and DNA damage genes.

    Evidence NMR structural analysis and RNA binding assays (S. pombe); siRNA knockdown with genome-wide splicing and expression analysis, live-cell imaging (human cells)

    PMID:24675469 PMID:25263959

    Open questions at the time
    • Whether RNA binding by the Myb domain is required for human CDC5L splicing function was not tested
    • Specific mis-spliced transcripts causally responsible for mitotic phenotype not individually validated
  11. 2015 Medium

    CTNNBL1 was established as a chaperone for the Prp19 complex by showing it enhances CWC15-CDC5L association and maintains Prp19 complex levels in vivo, with overlapping binding sites suggesting a dynamic exchange mechanism.

    Evidence Crosslinking and HDX mass spectrometry, in vitro binding assays, in vivo complex level analysis

    PMID:26130721

    Open questions at the time
    • Whether CTNNBL1 chaperone activity is catalytic or stoichiometric unclear
    • Kinetics of CWC15/CTNNBL1 exchange on CDC5L not measured
  12. 2021 Medium

    CDC5L was shown to directly bind specific pre-mRNA targets (Sox9, Col2a1, Wee1) and regulate their splicing to promote chondrogenesis and G2/M transition, demonstrating transcript-selective splicing control in a developmental context.

    Evidence RIP assay, siRNA knockdown, splicing efficiency analysis, cartilage rudiment growth assay

    PMID:34298017

    Open questions at the time
    • Binding specificity determinants (sequence or structure) on target pre-mRNAs unknown
    • Whether CDC5L binds these RNAs directly or as part of the Prp19 complex not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of CDC5L within the activated spliceosome, whether CDC5L's ATR checkpoint function is mechanistically separable from its splicing role, and the rules governing transcript-selective RNA binding by CDC5L's Myb-like domain.
  • No high-resolution structure of CDC5L within the human spliceosome
  • Separation-of-function mutants distinguishing splicing from checkpoint roles not generated
  • RNA-binding specificity rules for CDC5L not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 3 GO:0003723 RNA binding 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 2
Partners
ATRCTNNBL1HNRNPMPLRG1PPP1R8PRL1PRPF19SPF27
Complex memberships
Prp19/CDC5L complex (NTC)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Human CDC5L is a core component of a multiprotein spliceosomal complex (the CDC5L complex) that incorporates into the spliceosome in an ATP-dependent step and is required for the second catalytic step of pre-mRNA splicing. Immunodepletion of CDC5L from HeLa nuclear extract inhibits splicing product formation in vitro without preventing spliceosome assembly. Immunodepletion, in vitro splicing assay, mass spectrometry identification of complex components The EMBO journal High 11101529
2010 The human Prp19/CDC5L complex contains four copies of hPrp19 and has a stable core comprised of CDC5L, hPrp19, PRL1, and SPF27. SPF27 directly interacts with each core component. Limited proteolysis identified a protease-resistant sub-complex of SPF27, C-terminus of CDC5L, and N-termini of PRL1 and hPrp19. The complex adopts an elongated, asymmetric shape (~20 nm) under electron microscopy. Native complex purification, stoichiometric analysis, protein-protein interaction studies, limited proteolysis, electron microscopy Molecular and cellular biology High 20176811
2001 CDC5L directly interacts with PLRG1 in vitro and in vivo; the carboxyl-terminal region of CDC5L and the WD40 domain of PLRG1 mediate this interaction. Disrupting this interaction with a bacterially expressed CDC5L C-terminal domain fragment inhibits pre-mRNA splicing in HeLa nuclear extract. Co-immunoprecipitation, in vitro binding assay, domain mapping, in vitro splicing inhibition The Journal of biological chemistry High 11544257
1999 CDC5 proteins are required for pre-mRNA splicing. Mammalian CDC5 colocalizes with splicing factors, associates with core splicing machinery in nuclear extracts, interacts with the spliceosome throughout the splicing reaction in vitro, and genetic depletion of the yeast homolog CEF1 blocks the first step of pre-mRNA processing in vivo. Colocalization, co-immunoprecipitation from nuclear extracts, in vitro spliceosome interaction, yeast genetic depletion Proceedings of the National Academy of Sciences of the United States of America High 10570151
2000 The phosphorylation of CDC5L by cyclin E-Cdk2 is required for the interaction between the FHA domain of NIPP1 and CDC5L. CDC5L, NIPP1, and PP1 form a complex in rat liver nuclear extracts. The FHA domain of NIPP1 blocks beta-globin pre-mRNA splicing in nuclear extracts in a CDC5L-interaction-dependent manner. Yeast two-hybrid, co-immunoprecipitation, co-purification, in vitro splicing assay, FHA domain mutation The Journal of biological chemistry High 10827081
2009 CDC5L physically interacts with the checkpoint kinase ATR. Depletion of CDC5L by RNAi causes a defective S-phase cell-cycle checkpoint and cellular sensitivity to replication-fork blocking agents, and impairs activation of Chk1, Rad17, and FancD2 downstream of ATR. A CDC5L deletion mutant unable to interact with ATR fails to rescue the checkpoint deficiency. Co-immunoprecipitation, RNAi knockdown, checkpoint activation assays (Chk1/Rad17/FancD2 phosphorylation), deletion mutant rescue EMBO reports High 19633697
2008 Cell cycle-dependent phosphorylation of CDC5L at threonines 411 and 438 (CDK consensus sites) is required for CDC5L-mediated pre-mRNA splicing in vitro. CDC5L is phosphorylated on at least nine sites in vivo, and CDK2 inhibition blocks CDC5L phosphorylation both in vitro and in vivo. CDC5L forms homodimers in vitro and in vivo independently of phosphorylation. 2D phosphopeptide mapping, nanoelectrospray mass spectrometry, in vitro splicing assay, site-directed mutagenesis, CDK2 inhibitor treatment Cell cycle (Georgetown, Tex.) High 18583928
2011 CTNNBL1 binds the nuclear localization sequence (NLS) of CDC5L via its armadillo (ARM) domain, mediating CTNNBL1 association with the Prp19 complex. This interaction is distinct from canonical karyopherin-α NLS binding. Co-immunoprecipitation, domain mapping, NLS peptide binding assays The Journal of biological chemistry Medium 21385873
2015 CTNNBL1 enhances the association of CWC15 with CDC5L in vitro. In vivo, CTNNBL1 is required to maintain normal levels of the Prp19 complex and facilitate the interaction of CWC15 with CDC5L, acting as a chaperone for the essential Prp19 complex. An overlapping binding region on CDC5L suggests CTNNBL1 and CWC15 may exchange within the complex. Amine crosslinking and hydrogen-deuterium exchange mass spectrometry, in vitro binding assays, in vivo Prp19 complex level analysis Nucleic acids research Medium 26130721
2010 hnRNP-M directly interacts in vivo with CDC5L and PLRG1; a central region of hnRNP-M is required for this interaction. An hnRNP-M mutant lacking the CDC5L/PLRG1 interaction domain is unable to modulate alternative splicing of an adeno-E1A mini-gene substrate. The interaction is inhibited during heat-shock stress. Co-immunoprecipitation, domain mapping, alternative splicing reporter assay, heat-shock treatment EMBO reports Medium 20467437
2003 Peptides derived from the CDC5L C-terminal domain and PLRG1 WD40 interaction domains competitively inhibit pre-mRNA splicing in vitro. This inhibition is rescued by preincubating the peptides with their corresponding partner protein, confirming the CDC5L-PLRG1 interaction is essential for splicing. Peptide competition in vitro splicing assay, rescue with recombinant protein Nucleic acids research Medium 14576297
1998 Human CDC5 (CDC5L/hCdc5) positively regulates G2 progression and mitotic entry in mammalian cells. Overexpression shortens G2 and reduces cell size, while a dominant-negative mutant lacking the C-terminal activation domain delays G2 progression and mitotic entry. Overexpression and dominant-negative expression in mammalian cells, cell cycle analysis The Journal of biological chemistry Medium 9468527
2000 Human CDC5 binds specifically and with high affinity to a 12 bp DNA sequence through its amino terminus, and this DNA-protein interaction activates transcription in a reporter assay. A selection system in yeast identified human genomic sequences that interact with human CDC5 with similar specificity. In vitro DNA binding assay, transcription reporter assay, yeast selection system Journal of cell science Medium 11082045
2002 DAP-like kinase (Dlk) interacts with rat CDC5 in vitro; rat CDC5 is phosphorylated not by Dlk but by associated CK2 kinase in this complex. The interaction domain of CDC5 was mapped to the C-terminal region (residues 500-802). Both proteins co-localize in nuclear speckles in vivo. In vitro complex formation, kinase assay, domain mapping, co-localization by immunofluorescence Nucleic acids research Medium 11884640
2010 PRP19α/14-3-3β/CDC5L complex formation is regulated by Akt during NGF-induced neuronal differentiation of PC12 cells. Phosphorylation of PRP19α at Thr193 by Akt is critical for PRP19α binding with 14-3-3β, nuclear translocation, and PRP19α/14-3-3β/CDC5L complex formation. Co-immunoprecipitation, phosphorylation site mutagenesis, dominant-negative mutant expression, neuronal differentiation assay Journal of neuroscience research Medium 20629186
2014 Depletion of Cdc5L causes mitotic arrest, chromosome misalignments, sustained spindle assembly checkpoint activation, impaired kinetochore-microtubule attachment, and DNA damage, leading to mitotic catastrophe. Genome-wide analysis revealed Cdc5L modulates expression and pre-mRNA splicing efficiency of genes involved in mitosis and DNA damage response. siRNA knockdown, flow cytometry, live-cell imaging, chromosome alignment analysis, genome-wide gene expression and splicing analysis Cell death & disease Medium 24675469
2021 CDC5L promotes early chondrogenesis by directly binding target gene transcripts (Sox9, Col2a1, Wee1 pre-mRNAs) and modulating their splicing. Knockdown of Cdc5l decreased Sox9 and Col2a1 expression, enhanced Wee1 expression, blocked G2/M transition, and decreased cartilage matrix production. RNA-binding protein immunoprecipitation confirmed direct Cdc5l binding to these transcripts. siRNA knockdown, RIP assay, pre-mRNA splicing efficiency analysis, flow cytometry, cartilage rudiment growth assay The Journal of biological chemistry Medium 34298017
2012 CEF1 (yeast homolog of CDC5) alleles in the NTC (Prp19 complex) modulate transitions between catalytic conformations of the spliceosome. The myb-like domain of Cef1/CDC5 participates in interactions that stabilize the second-step spliceosome and affect splice site choice, resulting in alternative splicing-like patterns. Genetic suppressor analysis, in vitro splicing assay, genetic interaction studies with prp8 and U6 snRNA alleles RNA (New York, N.Y.) Medium 22408182
2014 The N-terminus of S. pombe Cdc5 (containing Myb repeats R1, R2, and domain D3) is required for Cdc5 function in vivo. The N-terminus binds RNA in vitro; D3 specifically binds double-stranded RNA despite not adopting a canonical Myb fold. NMR/structural analysis showed D3 has a distinct fold. Yeast genetics, RNA binding assays, NMR structural analysis Biochemistry Medium 25263959
2017 Prp19 regulates Cdc5L protein levels in HCC cells by repressing Cdc5L mRNA translation and facilitating lysosome-mediated degradation of Cdc5L protein. Silencing Prp19-induced G2/M arrest could be partially rescued by Cdc5L overexpression, placing Cdc5L downstream of Prp19 in mitotic progression. siRNA knockdown, overexpression rescue, Western blot, flow cytometry International journal of molecular sciences Low 28387715
2003 hLodestar/HuF2 interacts with CDC5L in yeast two-hybrid and HeLa nuclear extract co-immunoprecipitation. A truncated hLodestar/HuF2 polypeptide overlapping the CDC5L-binding region inhibits pre-mRNA splicing by disrupting spliceosome assembly. Yeast two-hybrid, co-immunoprecipitation from nuclear extract, in vitro splicing inhibition assay Biochemical and biophysical research communications Low 12927788
2003 Human CDC5 nuclear import is directed by its amino-terminus independently of canonical nuclear localization signals or phosphorylation; the carboxyl-terminus preferentially associates with spliceosomal complexes in proximity to RNA transcription during interphase. hCDC5 colocalizes with Sm proteins in a cell cycle- and domain-dependent manner. Domain deletion analysis, immunofluorescence colocalization, cell fractionation Cell biochemistry and biophysics Low 14515018

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 CDC5 and CKII control adaptation to the yeast DNA damage checkpoint. Cell 369 9323137
2001 Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast. Cell 310 11371343
1994 Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5. Journal of cell science 259 7962193
1993 A multicopy suppressor gene of the Saccharomyces cerevisiae G1 cell cycle mutant gene dbf4 encodes a protein kinase and is identified as CDC5. Molecular and cellular biology 237 8321244
2001 Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell 225 11733064
1998 The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae. Current biology : CB 217 9560342
2003 Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation. Science (New York, N.Y.) 208 12663816
2003 Polo-like kinase Cdc5 promotes chiasmata formation and cosegregation of sister centromeres at meiosis I. Nature cell biology 182 12717442
2000 Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry. The EMBO journal 179 11101529
1997 Plk is a functional homolog of Saccharomyces cerevisiae Cdc5, and elevated Plk activity induces multiple septation structures. Molecular and cellular biology 165 9154840
2008 Polo-like kinase Cdc5 drives exit from pachytene during budding yeast meiosis. Genes & development 149 18832066
2000 Essential function of the polo box of Cdc5 in subcellular localization and induction of cytokinetic structures. Molecular and cellular biology 141 10594031
2001 Order of function of the budding-yeast mitotic exit-network proteins Tem1, Cdc15, Mob1, Dbf2, and Cdc5. Current biology : CB 133 11378390
2006 Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis. Science (New York, N.Y.) 129 16763112
2013 CDC5, a DNA binding protein, positively regulates posttranscriptional processing and/or transcription of primary microRNA transcripts. Proceedings of the National Academy of Sciences of the United States of America 118 24101471
2013 Premature Cdk1/Cdc5/Mus81 pathway activation induces aberrant replication and deleterious crossover. The EMBO journal 114 23531881
2010 Molecular architecture of the human Prp19/CDC5L complex. Molecular and cellular biology 112 20176811
2001 A novel function of Saccharomyces cerevisiae CDC5 in cytokinesis. The Journal of cell biology 110 11157974
2000 NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry. The Journal of biological chemistry 95 10827081
1994 The Schizosaccharomyces pombe cdc5+ gene encodes an essential protein with homology to c-Myb. The EMBO journal 86 8313892
2009 Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint. EMBO reports 83 19633697
2003 The role of the polo kinase Cdc5 in controlling Cdc14 localization. Molecular biology of the cell 82 14551257
2018 Oncogenic Properties of NEAT1 in Prostate Cancer Cells Depend on the CDC5L-AGRN Transcriptional Regulation Circuit. Cancer research 81 29871935
2003 In vitro regulation of budding yeast Bfa1/Bub2 GAP activity by Cdc5. The Journal of biological chemistry 81 12637549
2008 APC/C-Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus. Genes & development 74 18172166
2008 Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. Molecular cancer research : MCR 74 18567798
1999 Evidence that Myb-related CDC5 proteins are required for pre-mRNA splicing. Proceedings of the National Academy of Sciences of the United States of America 69 10570151
1996 A cdc5+ homolog of a higher plant, Arabidopsis thaliana. Proceedings of the National Academy of Sciences of the United States of America 66 8917598
2014 Depletion of pre-mRNA splicing factor Cdc5L inhibits mitotic progression and triggers mitotic catastrophe. Cell death & disease 65 24675469
2002 Cdc5 influences phosphorylation of Net1 and disassembly of the RENT complex. BMC molecular biology 63 11960554
2005 Cdc28-dependent regulation of the Cdc5/Polo kinase. Current biology : CB 60 16303563
2010 Direct interaction between hnRNP-M and CDC5L/PLRG1 proteins affects alternative splice site choice. EMBO reports 59 20467437
1998 A mammalian homolog of fission yeast Cdc5 regulates G2 progression and mitotic entry. The Journal of biological chemistry 59 9468527
2002 Budding yeast Cdc5 phosphorylates Net1 and assists Cdc14 release from the nucleolus. Biochemical and biophysical research communications 57 12056824
2015 CEF1/OsMYB103L is involved in GA-mediated regulation of secondary wall biosynthesis in rice. Plant molecular biology 51 26350403
2013 Polo kinase Cdc5 is a central regulator of meiosis I. Proceedings of the National Academy of Sciences of the United States of America 50 23918381
2014 Digital expression profiling identifies RUNX2, CDC5L, MDM2, RECQL4, and CDK4 as potential predictive biomarkers for neo-adjuvant chemotherapy response in paediatric osteosarcoma. PloS one 49 24835790
1997 Pombe Cdc5-related protein. A putative human transcription factor implicated in mitogen-activated signaling. The Journal of biological chemistry 49 9038199
2010 CDC5 inhibits the hyperphosphorylation of the checkpoint kinase Rad53, leading to checkpoint adaptation. PLoS biology 48 20126259
2001 A direct interaction between the carboxyl-terminal region of CDC5L and the WD40 domain of PLRG1 is essential for pre-mRNA splicing. The Journal of biological chemistry 48 11544257
2001 Cdc5 interacts with the Wee1 kinase in budding yeast. Molecular and cellular biology 45 11438652
2020 Depletion of CDC5L inhibits bladder cancer tumorigenesis. Journal of Cancer 42 31897231
2010 Elevated levels of the polo kinase Cdc5 override the Mec1/ATR checkpoint in budding yeast by acting at different steps of the signaling pathway. PLoS genetics 41 20098491
2000 Human Cdc5, a regulator of mitotic entry, can act as a site-specific DNA binding protein. Journal of cell science 38 11082045
2020 Circ-PGAM1 promotes malignant progression of epithelial ovarian cancer through regulation of the miR-542-3p/CDC5L/PEAK1 pathway. Cancer medicine 36 32167655
2012 α-Synuclein disrupts stress signaling by inhibiting polo-like kinase Cdc5/Plk2. Proceedings of the National Academy of Sciences of the United States of America 36 22988096
2003 Loss of CDC5 function in Saccharomyces cerevisiae leads to defects in Swe1p regulation and Bfa1p/Bub2p-independent cytokinesis. Genetics 36 12586693
2008 Requirement for the budding yeast polo kinase Cdc5 in proper microtubule growth and dynamics. Eukaryotic cell 35 18178775
2011 CTNNBL1 is a novel nuclear localization sequence-binding protein that recognizes RNA-splicing factors CDC5L and Prp31. The Journal of biological chemistry 34 21385873
2020 Exo1 recruits Cdc5 polo kinase to MutLγ to ensure efficient meiotic crossover formation. Proceedings of the National Academy of Sciences of the United States of America 33 33199619
2010 Dbf4 regulates the Cdc5 Polo-like kinase through a distinct non-canonical binding interaction. The Journal of biological chemistry 33 21036905
2014 The yeast polo kinase Cdc5 regulates the shape of the mitotic nucleus. Current biology : CB 32 25454593
1998 Rearrangement of the human CDC5L gene by a t(6;19)(p21;q13.1) in a patient with multicystic renal dysplasia. Genomics 30 9598309
2017 Functions and regulation of the Polo-like kinase Cdc5 in the absence and presence of DNA damage. Current genetics 29 28770345
2009 The yeast SUMO isopeptidase Smt4/Ulp2 and the polo kinase Cdc5 act in an opposing fashion to regulate sumoylation in mitosis and cohesion at centromeres. Cell cycle (Georgetown, Tex.) 29 19823017
2017 CDC5L Promotes hTERT Expression and Colorectal Tumor Growth. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 27 28472785
2015 Expression and Clinical Role of Cdc5L as a Novel Cell Cycle Protein in Hepatocellular Carcinoma. Digestive diseases and sciences 26 26553251
2011 The budding yeast polo-like kinase Cdc5 regulates the Ndt80 branch of the meiotic recombination checkpoint pathway. Molecular biology of the cell 26 21795394
2011 Independent modulation of the kinase and polo-box activities of Cdc5 protein unravels unique roles in the maintenance of genome stability. Proceedings of the National Academy of Sciences of the United States of America 26 21987786
2010 Cell cycle-dependent phosphorylation of Rad53 kinase by Cdc5 and Cdc28 modulates checkpoint adaptation. Cell cycle (Georgetown, Tex.) 26 20046099
2008 Cell cycle-dependent phosphorylation of human CDC5 regulates RNA processing. Cell cycle (Georgetown, Tex.) 24 18583928
2015 Expression of CDC5L is associated with tumor progression in gliomas. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 26490980
2008 The Polo-like kinase Cdc5 interacts with FEAR network components and Cdc14. Cell cycle (Georgetown, Tex.) 23 18927509
2016 Mitotic Exit Function of Polo-like Kinase Cdc5 Is Dependent on Sequential Activation by Cdk1. Cell reports 22 27210759
2017 Prp19 Arrests Cell Cycle via Cdc5L in Hepatocellular Carcinoma Cells. International journal of molecular sciences 21 28387715
2012 Cdc5-dependent asymmetric localization of bfa1 fine-tunes timely mitotic exit. PLoS genetics 21 22253605
2009 The molecular function of the yeast polo-like kinase Cdc5 in Cdc14 release during early anaphase. Molecular biology of the cell 21 19570916
2003 Identification of peptide inhibitors of pre-mRNA splicing derived from the essential interaction domains of CDC5L and PLRG1. Nucleic acids research 21 14576297
2019 Cell cycle-dependent association of polo kinase Cdc5 with CENP-A contributes to faithful chromosome segregation in budding yeast. Molecular biology of the cell 20 30726152
2016 Polo kinase Cdc5 associates with centromeres to facilitate the removal of centromeric cohesin during mitosis. Molecular biology of the cell 19 27226485
2002 DAP-like kinase interacts with the rat homolog of Schizosaccharomyces pombe CDC5 protein, a factor involved in pre-mRNA splicing and required for G2/M phase transition. Nucleic acids research 19 11884640
2016 Centrosome-Dependent Bypass of the DNA Damage Checkpoint by the Polo Kinase Cdc5. Cell reports 17 26832404
2015 CTNNBL1 facilitates the association of CWC15 with CDC5L and is required to maintain the abundance of the Prp19 spliceosomal complex. Nucleic acids research 17 26130721
2014 The budding yeast Polo-like kinase Cdc5 is released from the nucleus during anaphase for timely mitotic exit. Cell cycle (Georgetown, Tex.) 17 25485506
2012 CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome. RNA (New York, N.Y.) 17 22408182
2024 MYB Transcription Factor CDC5 Activates CBF3 Expression to Positively Regulate Freezing Tolerance via Cooperating With ICE1 and Histone Modification in Arabidopsis. Plant, cell & environment 16 39248548
2021 Downregulation of DEAD-box helicase 21 (DDX21) inhibits proliferation, cell cycle, and tumor growth in colorectal cancer via targeting cell division cycle 5-like (CDC5L). Bioengineered 16 34903139
2020 ANXA7 promotes the cell cycle, proliferation and cell adhesion-mediated drug resistance of multiple myeloma cells by up-regulating CDC5L. Aging 16 32526706
2020 Long Noncoding RNA LINC00963 Promotes CDC5L-Mediated Malignant Progression in Gastric Cancer. OncoTargets and therapy 16 33376349
1981 Elevated recombination and pairing structures during meiotic arrest in yeast of the nuclear division mutant cdc5. Molecular & general genetics : MGG 16 7038388
2023 FOXA1 prolongs S phase and promotes cancer progression in non-small cell lung cancer through upregulation of CDC5L and activation of the ERK1/2 and JAK2 pathways. The Kaohsiung journal of medical sciences 15 37658700
2021 CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1. The Journal of biological chemistry 15 34298017
2016 Reduced kinase activity of polo kinase Cdc5 affects chromosome stability and DNA damage response in S. cerevisiae. Cell cycle (Georgetown, Tex.) 14 27565373
2003 hLodestar/HuF2 interacts with CDC5L and is involved in pre-mRNA splicing. Biochemical and biophysical research communications 14 12927788
1997 Differential expression of elongation factor-2, alpha4 phosphoprotein and Cdc5-like protein in prolactin-dependent/independent rat lymphoid cells. Molecular and cellular endocrinology 14 9296381
2020 Distinct surfaces on Cdc5/PLK Polo-box domain orchestrate combinatorial substrate recognition during cell division. Scientific reports 13 32099015
2004 A cDNA homologue of Schizosaccharomyces pombe cdc5(+) from the mushroom Lentinula edodes: characterization of the cDNA and its expressed product. Biochimica et biophysica acta 12 15488989
2010 Implication of Akt-dependent Prp19 alpha/14-3-3beta/Cdc5L complex formation in neuronal differentiation. Journal of neuroscience research 11 20629186
2003 Distinct domains of human CDC5 direct its nuclear import and association with the spliceosome. Cell biochemistry and biophysics 10 14515018
2014 Structural and functional insights into the N-terminus of Schizosaccharomyces pombe Cdc5. Biochemistry 9 25263959
2008 Basidiomycete Lentinula edodes CDC5 and a novel interacting protein CIPB bind to a newly isolated target gene in an unusual manner. Fungal genetics and biology : FG & B 9 18448367
2006 Adenoviral delivery of human CDC5 promotes G2/M progression and cell division in neonatal ventricular cardiomyocytes. Gene therapy 9 16482203
2016 Physical Association of Saccharomyces cerevisiae Polo-like Kinase Cdc5 with Chromosomal Cohesin Facilitates DNA Damage Response. The Journal of biological chemistry 8 27325700
2017 Polo-like kinase Cdc5 regulates Spc72 recruitment to spindle pole body in the methylotrophic yeast Ogataea polymorpha. eLife 7 28853395
2011 Phosphorylation of Cdc5 regulates its accumulation. Cell division 7 22204387
2006 Developmental regulator Le.CDC5 of the mushroom Lentinula edodes: analyses of its amount in each of the stages of fruiting-body formation and its distribution in parts of the fruiting bodies. FEMS microbiology letters 7 16842359
2024 m6A modification of CDC5L promotes lung adenocarcinoma progression through transcriptionally regulating WNT7B expression. American journal of cancer research 6 39113868
2024 IGF2BP1 promotes multiple myeloma with chromosome 1q gain via increasing CDC5L expression in an m6A-dependent manner. Genes & diseases 6 39534570
2010 Cdc5 blocks in vivo Rad53 activity, but not in situ activity (ISA). Cell cycle (Georgetown, Tex.) 6 20962588
2001 Prolactin, interleukin-2 and FGF-2 stimulate expression, nuclear distribution and DNA-binding of rat homolog of pombe Cdc5 in Nb2 T lymphoma cells. Molecular and cellular endocrinology 6 11694351