| First Author | Zhang J | Year | 2018 |
| Journal | Science | Volume | 361 |
| Issue | 6399 | Pages | 290-295 |
| PubMed ID | 30026228 | Mgi Jnum | J:358353 |
| Mgi Id | MGI:6191936 | Doi | 10.1126/science.aap8411 |
| Citation | Zhang J, et al. (2018) VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma. Science 361(6399):290-295 |
| abstractText | 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 kappaB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC. |
