Unknown

Dataset Information

0

Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF.


ABSTRACT: Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS through the transcriptional activation of p14ARF followed by p53 activation. Although the oncogene-mediated transcriptional regulation of p14ARF has been well addressed, the post-translational modification of p14ARF regulated by oncogenic stress has yet to be investigated. Here, we found that c-Myc increased p14ARF protein stability by inducing the transcription of ubiquitin-specific protease 10 (USP10). USP10, in turn, mediated the deubiquitination of p14ARF, preventing its proteasome-dependent degradation. USP10-null mouse embryonic fibroblasts and human primary cells depleted of USP10 bypassed c-Myc-induced senescence via the destabilization of p14ARF, and these cells displayed accelerated hyper-proliferation and transformation. Clinically the c-Myc-USP10-p14ARF axis was disrupted in non-small cell lung cancer patients, resulting in significantly worse overall survival. Our studies indicate that USP10 induced by c-Myc has a crucial role in OIS by maintaining the stability of key tumor suppressor p14ARF.

SUBMITTER: Ko A 

PROVIDER: S-EPMC5988833 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF.

Ko Aram A   Han Su Yeon SY   Choi Chel Hun CH   Cho Hanbyoul H   Lee Min-Sik MS   Kim Soo-Youl SY   Song Joon Seon JS   Hong Kyeong-Man KM   Lee Han-Woong HW   Hewitt Stephen M SM   Chung Joon-Yong JY   Song Jaewhan J  

Cell death and differentiation 20180222 6


Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS through the transcriptional activation of p14ARF followed by p53 activation. Although the oncogene-mediated transcriptional regulation of p14ARF has been well addressed, the post-translational modification of p14ARF regulated by oncogenic stress has yet to be investigated. Here, we found that c-Myc increased p14ARF protein stability by ind  ...[more]

Shared Molecules

Only show the datasets with similarity scores above: 0.5
     

Similar Datasets

| S-EPMC4007576 | biostudies-literature
| S-EPMC4836875 | biostudies-literature
| S-EPMC5125238 | biostudies-literature
| S-EPMC5133830 | biostudies-literature
| S-EPMC3981146 | biostudies-literature
| S-EPMC10111703 | biostudies-literature
| S-EPMC9830507 | biostudies-literature
| S-EPMC11370014 | biostudies-literature
| S-EPMC6954888 | biostudies-literature
| S-EPMC3808965 | biostudies-literature