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, Zhenkun Lou

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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 during tumorigenic progression. We suggest that WSB1 is one of the key players of early oncogenic events through ATM degradation and destruction of the tumorigenesis barrier. Our work establishes an important mechanism of cancer development and progression in premalignant lesions.

Original languageEnglish (US)
Pages (from-to)274-293
Number of pages20
JournalCell Research
Issue number2
StatePublished - Feb 1 2017


  • ATM
  • WD repeat and SOCS box-containing protein 1 (WSB1)
  • oncogene-induced senescence (OIS)
  • tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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