CDC73
Parafibromin (Cell division cycle protein 73 homolog) (Hyperparathyroidism 2 protein) [C1orf28] [HRPT2]
Publications[править]
Dysregulated gene expression is another important contributor in explaining cancer-related phenotypes in addition to mutations. Cellular senescence is a mechanism for the prevention of cancer and thus it is important to understand the regulation of gene expression in senescence due to its potential in anti-cancer therapy. Here, we found that CDC73, which encodes the cell division cycle 73 and acts as a tumor suppressor, was unexpectedly up-regulated in several cancer types but down-regulated in a variety of senescent cells. Importantly, depletion of CDC73 could induce senescence-associated phenotypes in both normal and cancer cells, with an increase in p21 expression. In terms of molecular mechanism, alternative polyadenylation (APA)-mediated 3' untranslated region (3' UTR) lengthening explained, at least in part, the decreased CDC73 expression in senescent cells because longer 3' UTR had a higher rate of RNA degradation compared to the shorter one. Our work discovered that post-transcriptional down-regulation of CDC73 contributed to cellular senescence.
MeSH Terms
- 3' Untranslated Regions
- Base Sequence
- Cell Line
- Cellular Senescence
- Cyclin-Dependent Kinase Inhibitor p21
- Down-Regulation
- Gene Expression Regulation, Neoplastic
- Gene Knockdown Techniques
- Humans
- Neoplasms
- Tumor Suppressor Proteins
- Up-Regulation
Keywords
- 3′ UTR
- CDC73
- Cancer
- Cellular senescence
- Gene expression