Property Summary

NCBI Gene PubMed Count 99
PubMed Score 321.58
PubTator Score 180.08

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (17)

Disease log2 FC p
malignant mesothelioma 2.000 1.6e-07
group 3 medulloblastoma 1.900 2.9e-03
atypical teratoid/rhabdoid tumor 1.600 4.4e-05
medulloblastoma, large-cell 1.900 1.4e-04
Atopic dermatitis 1.400 2.0e-03
adrenocortical carcinoma 1.609 7.0e-04
non-small cell lung cancer 2.392 4.3e-22
lung cancer 2.900 2.9e-06
active Crohn's disease 1.029 8.9e-03
pancreatic cancer 1.100 9.4e-04
lung adenocarcinoma 2.000 1.9e-10
nasopharyngeal carcinoma 1.200 3.7e-04
psoriasis 1.800 1.2e-140
Endometriosis 1.276 4.8e-02
inflammatory breast cancer 2.300 8.8e-04
ulcerative colitis 1.100 2.6e-04
ovarian cancer 1.100 3.4e-03

Gene RIF (69)

PMID Text
26818844 CDC6 and Cyclin F interact through defined sequence motifs that promote CDC6 ubiquitylation and degradation.
25875233 Cdc6 interacts with centrosomes during mitotic cell division.
25498505 The cell cycle-dependent centrosomal localization of Cdc6 in S and G2 phases suggest a novel function of Cdc6 in centrosomes.
25100863 The current study suggests that miR26a, miR26b, and CDC6 and factors regulating their expression represent potential cancer diagnostic and prognostic markers as well as anticancer targets.
24774443 Aberrant expression of both cyclin D1 and CDC6 by YB-1 over-expression may collaboratively participate in lung carcinogenesis.
24583551 These results provided new evidence for the regulatory mechanism of aberrant CDC6 oncogene transcription by FOXM1 and AR, two highly expressed transcription factors in prostate cancer cells
24434580 Cdk1 contributes to the nuclear export of Cdc6 at the S-to-G2 transition.
24216307 Two nuclear export signals of Cdc6 work cooperatively and distinctly for the cytoplasmic translocation of Cdc6 phosphorylated by cyclin A/Cdk2.
23803736 ORC/Cdc6/MCM2-7 complex is a new regulatory mechanism for the helicase.
23597704 the Nedd8 E1 inhibitor MLN4924 increased CDC6 protein expression due to a delay in cell cycle progression from G1 to S phase, resulting in accumulation of cells with high CDC6 protein levels.
23479742 the up-regulation of CDK2 by CUL4B is achieved via the repression of miR-372 and miR-373, which target CDK2.
23129444 The phosphorylation of S74 in Cdc6 could be important for binding to the nuclear export protein for cytoplasmic translocalization.
23011157 CDC6 and GDF-9 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.
22974333 Downregulation of Cdc6 effectively inhibits the proliferation of Tca8113 cells.
22908236 The Cdc6 is the AAA+ ATPase that assembles prereplicative complexes on replication origins in eukaryotic chromosomes and two more functions in mammalian cells to promote cell proliferation and survival.
22871742 Ectopic GATA1 stimulates endogenous CDC6 expression in hematopoietic and non-hematopoietic cells.
22589552 Data show that purified Epstein-Barr nuclear antigen 1 EBNA1 recruits purified Human Orc1 and Cdc6 onto replication origin oriP.
22523071 novel role for CDC6 in abetting the oncogenic sabotage carried out by HBx and support the paradigm that pre-replicative complex proteins have a role in oncogenic transformation.
22262174 Cdc6 protein was distributed around the spindle precursor at the time of germinal vesicle breakdown (GVBD), and localized to the margin of the nascent spindle early in prometaphase.
22223646 Cdc6 the AAA+ ATPase activated p27-bound Cdk2 in its ATPase and cyclin binding motif-dependent manner but only after the p27 bound to the Cdk2 was phosphorylated at the C terminus.
22201124 The Cdc6 acts as a molecular switch at the E-cadherin locus, linking transcriptional repression to activation of replication.
22179839 A novel mechanism of cdc6 regulation in which ATR can have a central role in inhibiting the initiation of DNA replication by the regulation of cdc6.
21519187 Phosphorylation of Cdc6 by polo-like kinase 1 (Plk1), one of the essential mitotic kinases, regulates mitotic exit.
21088490 Cdc6 expression is required for CDK2 chromatin association and kinase activation in stimulated primary human fibroblasts.
21048031 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
21041660 Plk1-mediated phosphorylation of Cdc6 promotes the interaction of Cdc6 and Cdk1, leading to the attenuation of Cdk1 activity, release of separase, and subsequent anaphase progression.
20813683 Norcantharidin can induce the degradation of Cdc6 in cancer cells to produce an anti-cancer effect.
20800603 Observational study of gene-disease association. (HuGE Navigator)
20606534 The CDC6 G1321A polymorphism may contribute to the risk of cervical cancer.
20606534 Observational study of gene-disease association. (HuGE Navigator)
20048340 Human CDC6 physically interacts with ATR, a crucial checkpoint kinase, in a manner that is stimulated by phosphorylation by Cdk and the CDC6-ATR interaction is conserved in Xenopus.
19950599 The expression of CDC6 was positively correlated with hMSH2 in cervical cancer.
19520769 peak androgen receptor occupancy at the novel androgen-response element occurs during the G1/S phase concomitant with peak Cdc6 mRNA expression.
19343071 GCN5 specifically acetylates CDC6 at three lysine residues flanking its cyclin-docking motif, and this modification is crucial for the subsequent phosphorylation of the protein by Cyclin A-CDKs at a specific residue close to the acetylation site.
19321444 The combination of st and deregulated cyclin E result in cooperative and coordinated activation of both an essential origin licensing factor, CDC6, and an activity required for origin firing, CDK2, resulting in progression from quiescence to S phase.
19233139 CDC6 may be one of the susceptibility genes that contribute to rapid decline in lung function despite smoking cessation in these patients with COPD.
19233139 Observational study of gene-disease association. (HuGE Navigator)
19189662 Cdc6 mRNA and protein had low expressions in normal oral mucosa but were highly expressed in precancerous lesions and oral squamous cell carcinoma.
19154794 The Cdc6 protein, a key DNA replication initiation factor, contributes to the long-term maintenance of the S-phase checkpoint by anchoring the Rad3-Rad26 complex to chromatin.
19107233 A hypothetical model whereby PTEN loss upregulates cell cycle genes such as cdc6 and cyclin E2 that in turn promote metastatic colonization at distant sites.
19101572 The Cdc6 G1321A polymorphism is associated with decreased risk of cancer.
19101572 Observational study of gene-disease association. (HuGE Navigator)
19074885 Observational study of gene-disease association. (HuGE Navigator)
18640135 Polymorphism in the Cdc6 promoter is associated with hepatocellular carcinoma
18640135 Observational study of gene-disease association. (HuGE Navigator)
18617514 rereplication-associated DNA damage triggers Cdt1 and Cdc6 ubiquitination and destruction; this pathway represents an evolutionarily conserved mechanism that minimizes the extent of rereplication
18458079 Cdc6 determines utilization of p21(WAF1/CIP1)-dependent damage checkpoint in S phase cells
18397887 PP2A can be targeted in a calcium-regulated manner to Cdc6 via the PR70 subunit, where it plays a role in regulating protein phosphorylation and stability.
18259842 Data suggest that human Cdc6 functions in several pathways to control the cell proliferation and the cell death.
18048387 deregulation of CDC6 expression in human cells poses a serious risk of carcinogenesis [review]
18006835 hCdt1 and hCdc6 expression promote malignant behavior
17689530 Cdc6 plays a key role in the sequential molecular events leading to repression of origin licensing and loss of proliferative capacity during execution of the differentiation programme.
17567951 These findings demonstrate an important and conserved role for Huwe1 in regulating Cdc6 abundance after DNA damage.
16801388 Truncated Cdc6 proteins act as dominant-negative inhibitors of replication initiation and disrupt chromatin structure and/or induce DNA damage, leading to ATM/ATR kinase activation and p53-Bax-mediated apoptosis
16572177 aberrant expression of Cdc6 is oncogenic by directly repressing the INK4/ARF locus through the RD(INK4/ARF) element
16439999 Cdc6 is not only required for G1 origin licensing, but is also crucial for proper S-phase DNA replication that is essential for DNA segregation during mitosis
16055707 initiation of DNA replication is regulated by p53 through Cdc6 protein stability
15887248 Androgen receptor may play important role in onset of DNA synthesis in prostate cancer cells by regulating expression and stability of Cdc6, critically required for assembly of pre-replication complex.
15696126 Results further confirm the importance of CDC6 in malignant transformation and in the pathogenesis of cervical dysplasia.
15590906 Cdc6 expression is regulated during megakaryocytic differentiation through transcriptional mechanisms involving a novel E2 box-GATA element.
15050687 When expressed in astrocytes, neurons, and non-glial 293T cells, HIV-1 Tat interacts with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA
14749377 endogenous Cdc6 remains nuclear and chromatin bound throughout the entire S period
14517333 caspase-mediated cleavage of Cdc6 creates a truncated Cdc6 fragment that is retained in the nucleus and induces apoptosis
12554670 Data show that human Cdc6 (HuCdc6) regulates the onset of mitosis, as overexpression of HuCdc6 in G(2) phase cells prevents entry into mitosis.
12429841 Results show that geminin, cdt1 and cdc6 are differentially regulated during megakaryocytic differentiation and suggest an active role of cdc6 in endomitosis.
12151338 HuCdc6 is cleaved by caspase 3 during apoptosis to prevent a wounded cell from replicating and to facilitate death
12006585 downregulation in prostate cancer
11846807 CHROMATIN CELLL CYCLE
11779870 Nuclear organization of DNA replication initiation proteins

AA Sequence

MPQTRSQAQATISFPKRKLSRALNKAKNSSDAKLEPTNVQTVTCSPRVKALPLSPRKRLGDDNLCNTPHL      1 - 70
PPCSPPKQGKKENGPPHSHTLKGRRLVFDNQLTIKSPSKRELAKVHQNKILSSVRKSQEITTNSEQRCPL     71 - 140
KKESACVRLFKQEGTCYQQAKLVLNTAVPDRLPAREREMDVIRNFLREHICGKKAGSLYLSGAPGTGKTA    141 - 210
CLSRILQDLKKELKGFKTIMLNCMSLRTAQAVFPAIAQEICQEEVSRPAGKDMMRKLEKHMTAEKGPMIV    211 - 280
LVLDEMDQLDSKGQDVLYTLFEWPWLSNSHLVLIGIANTLDLTDRILPRLQAREKCKPQLLNFPPYTRNQ    281 - 350
IVTILQDRLNQVSRDQVLDNAAVQFCARKVSAVSGDVRKALDVCRRAIEIVESDVKSQTILKPLSECKSP    351 - 420
SEPLIPKRVGLIHISQVISEVDGNRMTLSQEGAQDSFPLQQKILVCSLMLLIRQLKIKEVTLGKLYEAYS    421 - 490
KVCRKQQVAAVDQSECLSLSGLLEARGILGLKRNKETRLTKVFFKIEEKEIEHALKDKALIGNILATGLP    491 - 560
//

Text Mined References (105)

PMID Year Title
26818844 2016 SCF(Cyclin F)-dependent degradation of CDC6 suppresses DNA re-replication.
26201719 2015 Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts.
25875233 2015 Spatio-temporal regulation of the human licensing factor Cdc6 in replication and mitosis.
25498505 2015 Cdc6 localizes to S- and G2-phase centrosomes in a cell cycle-dependent manner.
25241761 2014 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
25100863 2014 MicroRNA-26a/b regulate DNA replication licensing, tumorigenesis, and prognosis by targeting CDC6 in lung cancer.
24774443 2014 YB-1 promotes transcription of cyclin D1 in human non-small-cell lung cancers.
24583551 2014 FOXM1 and androgen receptor co-regulate CDC6 gene transcription and DNA replication in prostate cancer cells.
24434580 2014 PIP-box-mediated degradation prohibits re-accumulation of Cdc6 during S phase.
24216307 2014 Two nuclear export signals of Cdc6 are differentially associated with CDK-mediated phosphorylation residues for cytoplasmic translocation.
23803736 2013 The ORC/Cdc6/MCM2–7 complex, a new power player for regulated helicase loading.
23711367 2013 A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and Nod2-mediated inflammatory responses.
23597704 2013 Destabilization of CDC6 upon DNA damage is dependent on neddylation but independent of Cullin E3 ligases.
23479742 2013 CUL4B promotes replication licensing by up-regulating the CDK2-CDC6 cascade.
23397142 2013 Analysis of protein-protein interactions in cross-talk pathways reveals CRKL protein as a novel prognostic marker in hepatocellular carcinoma.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23129444 2013 Phosphorylation of Cdc6 at serine 74, but not at serine 106, drives translocation of Cdc6 to the cytoplasm.
23011157 2012 Expression of CDC6 and GDF-9 and their clinicopathological significances in benign and malignant lesions of the gallbladder.
22974333 2013 Knockdown of Cdc6 inhibits proliferation of tongue squamous cell carcinoma Tca8113 cells.
22908236 2012 Cdc6: a trifunctional AAA+ ATPase that plays a central role in controlling the G(1)-S transition and cell survival.
22871742 2012 CDC6 expression is regulated by lineage-specific transcription factor GATA1.
22589552 2012 Epstein-Barr nuclear antigen 1 (EBNA1)-dependent recruitment of origin recognition complex (Orc) on oriP of Epstein-Barr virus with purified proteins: stimulation by Cdc6 through its direct interaction with EBNA1.
22523071 2012 HBx protein of hepatitis B virus promotes reinitiation of DNA replication by regulating expression and intracellular stability of replication licensing factor CDC6.
22262174 2012 Cdc6 is required for meiotic spindle assembly in Xenopus oocytes.
22223646 2012 Cdc6 protein activates p27KIP1-bound Cdk2 protein only after the bound p27 protein undergoes C-terminal phosphorylation.
22201124 2011 Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins.
22179839 2012 Hypoxic activation of ATR and the suppression of the initiation of DNA replication through cdc6 degradation.
21519187 2011 Regulation of the final stage of mitosis by components of the pre-replicative complex and a polo kinase.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21358632 2011 Mutations in the pre-replication complex cause Meier-Gorlin syndrome.
21088490 2010 Activation of Cdk2/Cyclin E complexes is dependent on the origin of replication licensing factor Cdc6 in mammalian cells.
21048031 2011 Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
21041660 2010 Cell division cycle 6, a mitotic substrate of polo-like kinase 1, regulates chromosomal segregation mediated by cyclin-dependent kinase 1 and separase.
20813683 2010 [Norcantharidin inhibits DNA replication initiation protein Cdc6 in cancer cells].
20800603 2010 Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
20606534 2010 Association between the CDC6 G1321A polymorphism and the risk of cervical cancer.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20048340 2010 CDC6 interaction with ATR regulates activation of a replication checkpoint in higher eukaryotic cells.
19950599 2009 [Expression and clinical significance of CDC6 and hMSH2 in cervical carcinoma].
19520769 2009 A novel androgen receptor-binding element modulates Cdc6 transcription in prostate cancer cells during cell-cycle progression.
19343071 2009 Acetylation by GCN5 regulates CDC6 phosphorylation in the S phase of the cell cycle.
19321444 2009 Coordinated activation of the origin licensing factor CDC6 and CDK2 in resting human fibroblasts expressing SV40 small T antigen and cyclin E.
19233139 2009 A novel polymorphism in CDC6 is associated with the decline in lung function of ex-smokers in COPD.
19189662 Expression of Mcm7 and Cdc6 in oral squamous cell carcinoma and precancerous lesions.
19154794 2009 ATR (AT mutated Rad3 related) activity stabilizes Cdc6 and delays G2/M-phase entry during hydroxyurea-induced S-phase arrest of HeLa cells.
19150984 2009 Identification and functional analysis of a novel cyclin e/cdk2 substrate ankrd17.
19107233 2009 Cdc6 and cyclin E2 are PTEN-regulated genes associated with human prostate cancer metastasis.
19101572 2009 Association analysis between the Cdc6 G1321A polymorphism and the risk for non-Hodgkin lymphoma and hepatocellular carcinoma.
19074885 2008 Genetic variants in apoptosis and immunoregulation-related genes are associated with risk of chronic lymphocytic leukemia.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18640135 2008 A novel functional polymorphism in the Cdc6 promoter is associated with the risk for hepatocellular carcinoma.
18617514 2008 Cdt1 and Cdc6 are destabilized by rereplication-induced DNA damage.
18458079 2008 Cdc6 determines utilization of p21(WAF1/CIP1)-dependent damage checkpoint in S phase cells.
18397887 2008 Protein phosphatase 2A is targeted to cell division control protein 6 by a calcium-binding regulatory subunit.
18259842 2008 Cdc6 knockdown inhibits human neuroblastoma cell proliferation.
18048387 2008 CDC6: from DNA replication to cell cycle checkpoints and oncogenesis.
18006835 2007 Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior.
17689530 2007 Cdc6 is a rate-limiting factor for proliferative capacity during HL60 cell differentiation.
17567951 2007 Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage.
16801388 2006 Cleavage of Cdc6 by caspase-3 promotes ATM/ATR kinase-mediated apoptosis of HeLa cells.
16572177 2006 Oncogenic activity of Cdc6 through repression of the INK4/ARF locus.
16439999 2006 The functional role of Cdc6 in S-G2/M in mammalian cells.
16055707 2005 p53-Dependent regulation of Cdc6 protein stability controls cellular proliferation.
15887248 2005 Androgen receptor regulates Cdc6 in synchronized LNCaP cells progressing from G1 to S phase.
15707391 2005 DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system.
15696126 2005 Quantitation of CDC6 and MCM5 mRNA in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix.
15590906 2004 A novel E2 box-GATA element modulates Cdc6 transcription during human cells polyploidization.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15232106 2004 Self-assembling protein microarrays.
15226314 2004 Human claspin is a ring-shaped DNA-binding protein with high affinity to branched DNA structures.
14749377 2004 Cdc6 chromatin affinity is unaffected by serine-54 phosphorylation, S-phase progression, and overexpression of cyclin A.
14672932 2004 The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells.
14517333 2003 Caspase-3-mediated cleavage of Cdc6 induces nuclear localization of p49-truncated Cdc6 and apoptosis.
12912926 2003 Localization of proteins bound to a replication origin of human DNA along the cell cycle.
12791985 2003 Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
12614612 2003 Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells.
12554670 2003 Human replication protein Cdc6 prevents mitosis through a checkpoint mechanism that implicates Chk1.
12538639 2003 HA95 and LAP2 beta mediate a novel chromatin-nuclear envelope interaction implicated in initiation of DNA replication.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12429841 2002 Regulation of CDC6, geminin, and CDT1 in human cells that undergo polyploidization.
12151338 2002 Human replication protein Cdc6 is selectively cleaved by caspase 3 during apoptosis.
12045100 2002 DNA replication in eukaryotic cells.
11931757 2002 Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication.
11846807 2002 Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell cycle.
11779870 2002 Nuclear organization of DNA replication initiation proteins in mammalian cells.
11346650 2001 Multiple mechanisms regulate subcellular localization of human CDC6.
11125146 2000 Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.
11095689 2000 The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase.
11046155 2000 Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.
10995389 2000 Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1.
10899308 2000 CDC6 interacts with c-Myc to inhibit E-box-dependent transcription by abrogating c-Myc/Max complex.
10629059 2000 PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells.
10464337 1999 Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation.
10436018 1999 The Cdc6 nucleotide-binding site regulates its activity in DNA replication in human cells.
10339564 1999 Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.
10214964 1999 Identification of the sequence responsible for the nuclear localization of human Cdc6.
9925618 1999 Changes in bacterial and eukaryotic community structure after mass lysis of filamentous cyanobacteria associated with viruses.
9889196 1999 Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
9857179 1998 Cdc6 protein causes premature entry into S phase in a mammalian cell-free system.
9778043 1998 Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F.
9774682 1998 Cell cycle-regulated expression of mammalian CDC6 is dependent on E2F.
9566895 1998 Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase.
9520412 1998 Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.
8990175 1997 A human protein related to yeast Cdc6p.