We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Hypoxia-induced proteasomal degradation of DBC1 by SIAH2 in breast cancer progression.
- Authors
Qiangqiang Liu; Qian Luo; Jianyu Feng; Yanping Zhao; Biao Ma; Hongcheng Cheng; Tian Zhao; Hong Lei; Chenglong Mu; Linbo Chen; Yuanyuan Meng; Jiaojiao Zhang; Yijia Long; Jingyi Su; Guo Chen; Yanjun Li; Gang Hu; Xudong Liao; Quan Chen; Yushan Zhu
- Abstract
DBC1 has been characterized as a key regulator of physiological and pathophysiological activities, such as DNA damage, senescence, and tumorigenesis. However, the mechanism by which the functional stability of DBC1 is regulated has yet to be elucidated. Here, we report that the ubiquitination-mediated degradation of DBC1 is regulated by the E3 ubiquitin ligase SIAH2 and deubiquitinase OTUD5 under hypoxic stress. Mechanistically, hypoxia promoted DBC1 to interact with SIAH2 but not OTUD5, resulting in the ubiquitination and subsequent degradation of DBC1 through the ubiquitin-proteasome pathway. SIAH2 knockout inhibited tumor cell proliferation and migration, which could be rescued by double knockout of SIAH2/CCAR2. Human tissue microarray analysis further revealed that the SIAH2/DBC1 axis was responsible for tumor progression under hypoxic stress. These findings define a key role of the hypoxia-mediated SIAH2-DBC1 pathway in the progression of human breast cancer and provide novel insights into the metastatic mechanism of breast cancer.
- Subjects
UBIQUITINATION; BREAST cancer; CANCER invasiveness; INHIBITION of cellular proliferation; DNA damage; TISSUE analysis
- Publication
eLife, 2022, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.81247