Title |
VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma
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Published in |
Science, July 2018
|
DOI | 10.1126/science.aap8411 |
Pubmed ID | |
Authors |
Jing Zhang, Tao Wu, Jeremy Simon, Mamoru Takada, Ryoichi Saito, Cheng Fan, Xian-De Liu, Eric Jonasch, Ling Xie, Xian Chen, Xiaosai Yao, Bin Tean Teh, Patrick Tan, Xingnan Zheng, Mingjie Li, Cortney Lawrence, Jie Fan, Jiang Geng, Xijuan Liu, Lianxin Hu, Jun Wang, Chengheng Liao, Kai Hong, Giada Zurlo, Joel S Parker, J Todd Auman, Charles M Perou, W Kimryn Rathmell, William Y Kim, Marc W Kirschner, William G Kaelin, Albert S Baldwin, Qing Zhang |
Abstract |
Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 52 | 71% |
Germany | 2 | 3% |
United Kingdom | 2 | 3% |
Spain | 1 | 1% |
Italy | 1 | 1% |
Argentina | 1 | 1% |
Brazil | 1 | 1% |
Chile | 1 | 1% |
Saudi Arabia | 1 | 1% |
Other | 0 | 0% |
Unknown | 11 | 15% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 38 | 52% |
Scientists | 26 | 36% |
Practitioners (doctors, other healthcare professionals) | 7 | 10% |
Unknown | 2 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 143 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 30 | 21% |
Student > Ph. D. Student | 29 | 20% |
Student > Master | 11 | 8% |
Student > Bachelor | 10 | 7% |
Student > Doctoral Student | 9 | 6% |
Other | 22 | 15% |
Unknown | 32 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 45 | 31% |
Medicine and Dentistry | 23 | 16% |
Agricultural and Biological Sciences | 21 | 15% |
Immunology and Microbiology | 6 | 4% |
Chemistry | 3 | 2% |
Other | 10 | 7% |
Unknown | 35 | 24% |