Редактирование: CDC6

Cell division control protein 6 homolog (CDC6-related protein) (Cdc18-related protein) (HsCdc18) (p62(cdc6)) (HsCDC6) [CDC18L]

==Publications==

{{medline-entry
|title=A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29321003
|abstract=Senescence is a fundamental biological process implicated in various pathologies, including cancer. Regarding carcinogenesis, senescence signifies, at least in its initial phases, an anti-tumor response that needs to be circumvented for cancer to progress. Micro-RNAs, a subclass of regulatory, non-coding RNAs, participate in senescence regulation. At the subcellular level micro-RNAs, similar to proteins, have been shown to traffic between organelles influencing cellular behavior. The differential function of micro-RNAs relative to their subcellular localization and their role in senescence biology raises concurrent in situ analysis of coding and non-coding gene products in senescent cells as a necessity. However, technical challenges have rendered in situ co-detection unfeasible until now. In the present report we describe a methodology that bypasses these technical limitations achieving for the first time simultaneous detection of both a micro-RNA and a protein in the biological context of cellular senescence, utilizing the new commercially available SenTraGor  compound. The method was applied in a prototypical human non-malignant epithelial model of oncogene-induced senescence that we generated for the purposes of the study. For the characterization of this novel system, we applied a wide range of cellular and molecular techniques, as well as high-throughput analysis of the transcriptome and micro-RNAs. This experimental setting has three advantages that are presented and discussed: i) it covers a "gap" in the molecular carcinogenesis field, as almost all corresponding in vitro models are fibroblast-based, even though the majority of neoplasms have epithelial origin, ii) it recapitulates the precancerous and cancerous phases of epithelial tumorigenesis within a short time frame under the light of natural selection and iii) it uses as an oncogenic signal, the replication licensing factor [[CDC6]], implicated in both DNA replication and transcription when over-expressed, a characteristic that can be exploited to monitor RNA dynamics. Consequently, we demonstrate that our model is optimal for studying the molecular basis of epithelial carcinogenesis shedding light on the tumor-initiating events. The latter may reveal novel molecular targets with clinical benefit. Besides, since this method can be incorporated in a wide range of low, medium or high-throughput image-based approaches, we expect it to be broadly applicable.
|mesh-terms=* Carcinogenesis
* Cell Cycle Proteins
* Cells, Cultured
* Cellular Senescence
* Epithelial Cells
* Gene Expression Profiling
* Genome
* Humans
* MicroRNAs
* Neoplasms, Glandular and Epithelial
* Nuclear Proteins
* Oncogenes
* Proteins
|keywords=* CDC6
* Cancer
* DNA damage response
* In situ hybridization
* Micro-RNAs
* Oncogene-induced senescence
* R loops
* Replication stress
* SenTraGorTM
* rDNA
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763532
}}
{{medline-entry
|title=ARF-induced downregulation of Mip130/LIN-9 protein levels mediates a positive feedback that leads to increased expression of p16Ink4a and p19Arf.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20101237
|abstract=The ARF-[[MDM2]]-p53 pathway constitutes one of the most important mechanisms of surveillance against oncogenic transformation, and its inactivation occurs in a large proportion of cancers. Here, we show that ARF regulates Mip130/LIN-9 by inducing its translocation to the nucleolus and decreasing the expression of the Mip130/LIN-9 protein through a post-transcriptional mechanism. The knockdown of Mip130/LIN-9 in p53(-/-) and Arf(-/-) mouse embryonic fibroblasts (MEFs) mimics some effects of ARF, such as the downregulation of B-Myb, impaired induction of G2/M genes, and a decrease in cell proliferation. Importantly, although the knockdown of Mip130/LIN-9 reduced the proliferation of p53 or Arf-null MEFs, only p53(-/-) MEFs showed a senescence-like state and an increase in the expression of Arf and p16. Interestingly, the increase in p16 and ARF is indirect because the Mip130/LIN-9 knockdown decreased the transcription of negative regulators of the Ink4a/Arf locus, such as BUBR1 and [[CDC6]]. Chromatin immunoprecipitation assays also reveal that Mip130/LIN-9 occupies the promoters of the BubR1 and cdc6 genes, suggesting that Mip130/LIN-9 is necessary for the expression of these genes. Altogether, these results indicate that there is a feedback mechanism between ARF and Mip130/LIN-9 in which either the increase of ARF or the decrease in Mip130/LIN-9 causes a further increase in the expression of Arf and p16.
|mesh-terms=* Aging
* Animals
* Cell Line, Transformed
* Cell Transformation, Neoplastic
* Cells, Cultured
* Cyclin-Dependent Kinase Inhibitor p16
* Down-Regulation
* Fibroblasts
* Genes, p53
* Humans
* Mice
* Mice, Knockout
* NIH 3T3 Cells
* Tumor Suppressor Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116813
}}