Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MicroRNAs (miRNAs) are small regulatory non-coding RNAs that have been reported to play an important role in a variety of cellular functions. Recent studies indicated that some miRNAs are involved in regulating endoplasmic reticulum (ER) stress adaptation. However, the miRNAs were still unknown in osteosarcoma. In this study, we demonstrated that miR-1281 induced by ER stress promoted cell apoptosis and decreased ER stress adaptation of osteosarcoma in vitro and in vivo. Further mechanistic studies revealed that p53, an important tumor suppressor, directly bound to the promoter of miR-1281, leading to its increase under ER stress. Additionally, our data suggest that USP39 was the target of miR-1281 and participated in ER stress-induced cell apoptosis. Thus, our findings suggest a new role for miR-1281 in osteosarcoma and suggest that the p53-dependent, miR-1281-mediated USP39 pathway inhibits the survival of human osteosarcoma cells under ER stress.
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PMID:MiR-1281, a p53-responsive microRNA, impairs the survival of human osteosarcoma cells upon ER stress via targeting USP39. 3032 69

The serine/threonine kinase, CHK2 (checkpoint kinase 2), is a key mediator in DNA damage response and a tumor suppressor, which is implicated in promoting cell cycle arrest, apoptosis and DNA repair. Accumulating evidence suggests that these functions are primarily exerted through phosphorylation downstream factors such as p53 and BRCA1. Recent studies have shown that ubiquitination is an important mode of regulation of CHK2. However, it remains largely unclear whether deubiquitinases participate in regulation of CHK2. Here, we report that a deubiquitinase, USP39, is a new regulator of CHK2. Mechanistically, USP39 deubiquitinates and stabilizes CHK2, which in turn enhances CHK2 stability. Short hairpin RNA (shRNA) mediated knockdown of USP39 led to deregulate CHK2, which resulted in compromising the DNA damage-induced G2/M checkpoint, decreasing apoptosis, and conferring cancer cells resistance to chemotherapy drugs and radiation treatment. Collectively, we identify USP39 as a novel regulator of CHK2 in the DNA damage response.
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PMID:USP39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing CHK2. 3077 28