Immunocytochemical staining of HepG2 cells with Phospho-CDC6 (Ser106) antibody. Nuclei were stained blue with DAPI; Phospho-CDC6 (Ser106) was stained magenta with Alexa Fluor? 647. Images were taken using Leica stellaris 5. Protein abundance based on laser Intensity and smart gain: Medium. Scale bar, 20 μm.
Western blotting analysis using phospho-CDC6 (Ser106) antibody. Total cell lysates (30 μg) from various cell lines were loaded and separated by SDS-PAGE. The blot was incubated with phospho-CDC6 (Ser106) antibody and HRP-conjugated goat anti-rabbit secondary antibody respectively.
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用途:
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Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
基因功能參考文獻:
DNA replication licensing factor Cdc6 is recruited to the proximal side of the centrioles via cyclin A to negatively regulate centrosome duplication by binding and inhibiting the cartwheel protein Sas-6 from forming a stable complex with another centriole duplication core protein, STIL. PMID: 28447620
Results show that both Cdc6 and Cdt1, when expressed in a high level, alone or in combination, were significantly associated with poorer survival in the breast cancer patient cohort. In line with this finding, the expression of Cdc6 and Cdt1 was upregulated in breast cancer cells compared to normal breast epithelial cells. Expression of Cdc6 and Cdt1 was significantly higher in ER negative breast cancer. PMID: 28428557
Results suggested that Cdc6 controls centrosome duplication in a manner independent of its recruitment of PCM proteins to the centrosome. PMID: 29237113
WHSC1L1 and H3K36me2 are enriched in the gene bodies of the cell cycle-related genes CDC6 and CDK2, implying that WHSC1L1 directly regulates the transcription of these gene PMID: 27285764
Cdc6 expression is up-regulated in bladder cancer tissues and is positively correlated to high tumor grade. PMID: 27246979
PPP2R3B codes for the PR70 protein, a regulatory substrate-recognizing subunit of protein phosphatase 2A. PR70 decreased melanoma growth by negatively interfering with DNA replication and cell cycle progression through its role in stabilizing CDC6-chromatin licensing and CDT1 interaction PMID: 27974665
Data suggest that regulation of microtubule nucleation and recruitment of pericentriolar proteins to centrosome requires Cdc6 ATPase activity, as well as centrosomal localization of Cdc6. PMID: 28827311
this study provides a novel regulatory signaling pathway of CDC6-regulated epithelial ovarian cancer growth PMID: 26920249
The data demonstrate that Cdc6 serves as a regulator of ribosomal DNA transcription initiation, and indicate a mechanism by which initiation of ribosomal DNA transcription and DNA replication can be coordinated in cells. PMID: 26872786
Cdc6 interacts with centrosomes during mitotic cell division. PMID: 25875233
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. PMID: 25100863
The cell cycle-dependent centrosomal localization of Cdc6 in S and G2 phases suggest a novel function of Cdc6 in centrosomes. PMID: 25498505
Cdk1 contributes to the nuclear export of Cdc6 at the S-to-G2 transition. PMID: 24434580
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. PMID: 22908236
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 PMID: 24583551
Two nuclear export signals of Cdc6 work cooperatively and distinctly for the cytoplasmic translocation of Cdc6 phosphorylated by cyclin A/Cdk2. PMID: 24216307
ORC/Cdc6/MCM2-7 complex is a new regulatory mechanism for the helicase. PMID: 23803736
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. PMID: 23597704
Downregulation of Cdc6 effectively inhibits the proliferation of Tca8113 cells. PMID: 22974333
Norcantharidin can induce the degradation of Cdc6 in cancer cells to produce an anti-cancer effect. PMID: 20813683
the up-regulation of CDK2 by CUL4B is achieved via the repression of miR-372 and miR-373, which target CDK2. PMID: 23479742
The phosphorylation of S74 in Cdc6 could be important for binding to the nuclear export protein for cytoplasmic translocalization. PMID: 23129444
CDC6 and GDF-9 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma. PMID: 23011157
Ectopic GATA1 stimulates endogenous CDC6 expression in hematopoietic and non-hematopoietic cells. PMID: 22871742
Data show that purified Epstein-Barr nuclear antigen 1 EBNA1 recruits purified Human Orc1 and Cdc6 onto replication origin oriP. PMID: 22589552
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. PMID: 22523071
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. PMID: 22262174
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. PMID: 22223646
Phosphorylation of Cdc6 by polo-like kinase 1 (Plk1), one of the essential mitotic kinases, regulates mitotic exit. PMID: 21519187
The Cdc6 acts as a molecular switch at the E-cadherin locus, linking transcriptional repression to activation of replication. PMID: 22201124
Cdc6 expression is required for CDK2 chromatin association and kinase activation in stimulated primary human fibroblasts. PMID: 21088490
The CDC6 G1321A polymorphism may contribute to the risk of cervical cancer. PMID: 20606534
The expression of CDC6 was positively correlated with hMSH2 in cervical cancer. PMID: 19950599
Nuclear organization of DNA replication initiation proteins PMID: 11779870
HuCdc6 is cleaved by caspase 3 during apoptosis to prevent a wounded cell from replicating and to facilitate death PMID: 12151338
Results show that geminin, cdt1 and cdc6 are differentially regulated during megakaryocytic differentiation and suggest an active role of cdc6 in endomitosis. PMID: 12429841
Data show that human Cdc6 (HuCdc6) regulates the onset of mitosis, as overexpression of HuCdc6 in G(2) phase cells prevents entry into mitosis. PMID: 12554670
caspase-mediated cleavage of Cdc6 creates a truncated Cdc6 fragment that is retained in the nucleus and induces apoptosis PMID: 14517333
endogenous Cdc6 remains nuclear and chromatin bound throughout the entire S period PMID: 14749377
Cdc6 expression is regulated during megakaryocytic differentiation through transcriptional mechanisms involving a novel E2 box-GATA element. PMID: 15590906
Results further confirm the importance of CDC6 in malignant transformation and in the pathogenesis of cervical dysplasia. PMID: 15696126
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. PMID: 15887248
initiation of DNA replication is regulated by p53 through Cdc6 protein stability PMID: 16055707
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 PMID: 16439999
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 PMID: 16801388
These findings demonstrate an important and conserved role for Huwe1 in regulating Cdc6 abundance after DNA damage. PMID: 17567951
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. PMID: 17689530
hCdt1 and hCdc6 expression promote malignant behavior PMID: 18006835