Transcriptional factor HBP1 targets P16INK4A, upregulating its expression and consequently is involved in Ras-induced premature senescence
نویسندگان
چکیده
منابع مشابه
PML is induced by oncogenic ras and promotes premature senescence.
Oncogenic ras provokes a senescent-like arrest in human diploid fibroblasts involving the Rb and p53 tumor suppressor pathways. To further characterize this response, we compared gene expression patterns between ras-arrested and quiescent IMR90 fibroblasts. One of the genes up-regulated during ras-induced arrest was promyelocytic leukemia (PML) protein, a potential tumor suppressor that encodes...
متن کاملOncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
Oncogenic ras can transform most immortal rodent cells to a tumorigenic state. However, transformation of primary cells by ras requires either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16. Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest. The arrest induced by ras is accompanied by accumulation ...
متن کاملRole of p16INK4A in Replicative Senescence and DNA Damage-Induced Premature Senescence in p53-Deficient Human Cells
The p16(INK4A) (hereafter p16) tumor suppressor is encoded by the INK4A/ARF locus which is among the most commonly dysregulated sequences in human cancer. By inhibiting cyclin-dependent kinases, p16 activates the G1-S checkpoint, and this response is often considered to be critical for establishing a senescence-like growth arrest. Not all studies support a universal role for p16 in senescence. ...
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The p16(INK4a)-Rb tumour suppressor pathway is required for the initiation and maintenance of cellular senescence, a state of permanent growth arrest that acts as a natural barrier against cancer progression. Senescence can be overcome if the pathway is not fully engaged, and this may occur when p16(INK4a) is inactivated. p16(INK4a) is frequently altered in human cancer and germline mutations a...
متن کاملThe acetylation of transcription factor HBP1 by p300/CBP enhances p16INK4A expression
HBP1 is a sequence-specific DNA-binding transcription factor with many important biological roles. It activates or represses the expression of some specific genes during cell growth and differentiation. Previous studies have exhibited that HBP1 binds to p16(INK4A) promoter and activates p16(INK4A) expression. We found that trichostatin A (TSA), an inhibitor of HDAC (histone deacetylase), induce...
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ژورنال
عنوان ژورنال: Oncogene
سال: 2010
ISSN: 0950-9232,1476-5594
DOI: 10.1038/onc.2010.252