Редактирование: HIC1 (раздел)

==Publications==

{{medline-entry
|title=Tumor suppressor [[HIC1]] directly regulates [[SIRT1]] to modulate p53-dependent DNA-damage responses.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16269335
|abstract=Hypermethylated in cancer 1 ([[HIC1]]) is an epigenetically regulated transcriptional repressor that functionally cooperates with p53 to suppress age-dependent development of cancer in mice. Here we show that the mechanism by which the loss of [[HIC1]] function promotes tumorigenesis is via activating the stress-controlling protein [[SIRT1]] and thereby attenuating p53 function. [[HIC1]] forms a transcriptional repression complex with [[SIRT1]] deacetylase, and this complex directly binds the [[SIRT1]] promoter and represses its transcription. Inactivation of [[HIC1]] results in upregulated [[SIRT1]] expression in normal or cancer cells; this deacetylates and inactivates p53, allowing cells to bypass apoptosis and survive DNA damage. Inhibition of [[SIRT1]] function in cells without [[HIC1]] abolishes the resistance to apoptosis. Since aging increases promoter hypermethylation and epigenetic silencing of [[HIC1]], we speculate that the resultant upregulation of [[SIRT1]] may be a double-edged sword that both promotes survival of aging cells and increases cancer risk in mammals.
|mesh-terms=* Adenocarcinoma
* Aging
* Animals
* Apoptosis
* Cell Line
* Cell Line, Tumor
* Chlorocebus aethiops
* DNA Damage
* Epigenesis, Genetic
* Humans
* Kruppel-Like Transcription Factors
* Lung Neoplasms
* Lymphoma
* Methylation
* Mice
* Promoter Regions, Genetic
* Protein Binding
* Protein Structure, Tertiary
* Sarcoma, Experimental
* Sirtuin 1
* Sirtuins
* Soft Tissue Neoplasms
* Transcription Factors
* Tumor Suppressor Protein p53
* Up-Regulation

|full-text-url=https://sci-hub.do/10.1016/j.cell.2005.08.011
}}
{{medline-entry
|title=Concordant methylation of the ER and N33 genes in glioblastoma multiforme.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9671399
|abstract=Methylation of promoter-associated CpG islands appears to be a potential way by which tumor suppressor genes are inactivated in cancer. Using Southern blot analysis, we have studied the methylation of several genes in glioblastoma multiforme (GBM), trying to determine their contribution to tumorigenesis. Genes studied included the estrogen receptor (ER), N33, the candidate tumor-suppressors P15, P16 and [[HIC1]] and a control gene, c-abl. Hypermethylation of N33, ER, [[HIC1]], P16, P15 and c-abl were found in 61%, 59%, 60%, 5%, 2% and 0% of GBM respectively. [[HIC1]] methylation was detected in normal brain as well, but appeared to be more extensive in tumors. ER and N33 methylation were significantly more frequent in tumors from individuals over the age of 40 (70% and 88% vs 36% and 14%). In addition, there was a strong association between ER and N33 methylation, which were concordant in 81% of the cases (P<0.01). ER and N33 methylation in GBM may therefore appear as a result of shared etiologic factors, which may relate in part to aging cell populations in the brain.
|mesh-terms=* Aging
* Base Sequence
* Brain
* Brain Neoplasms
* CpG Islands
* DNA Methylation
* DNA Primers
* Genes, Tumor Suppressor
* Glioblastoma
* Humans
* Receptors, Estrogen

|full-text-url=https://sci-hub.do/10.1038/sj.onc.1201831
}}