Volume 27, No 2, Feb 2017

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 27 Issue 2, February 2017: 274-293

ORIGINAL ARTICLES

WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation

Jung Jin Kim, Seung Baek Lee, Sang-Yeop Yi, Sang-Ah Han, Sun-Hyun Kim, Jong-Min Lee, Seo-Yun Tong, Ping Yin, Bowen Gao, Jun Zhang and Zhenkun Lou

Correspondence:

Oncogene-induced senescence (OIS) or apoptosis through the DNA-damage response is an important barrier of tumorigenesis. Overcoming this barrier leads to abnormal cell proliferation, genomic instability, and cellular transformation, and finally allows cancers to develop. However, it remains unclear how the OIS barrier is overcome. Here, we show that the E3 ubiquitin ligase WD repeat and SOCS box-containing protein 1 (WSB1) plays a role in overcoming OIS. WSB1 expression in primary cells helps the bypass of OIS, leading to abnormal proliferation and cellular transformation. Mechanistically, WSB1 promotes ATM ubiquitination, resulting in ATM degradation and the escape from OIS. Furthermore, we identify CDKs as the upstream kinase of WSB1. CDK-mediated phosphorylation activates WSB1 by promoting its monomerization. In human cancer tissue and in vitro models, WSB1-induced ATM degradation is an early event d

10.1038/cr.2016.148

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