|
| Status |
Public on Jul 19, 2018 |
| Title |
VHL Substrate Transcription Factor ZHX2 As An Oncogenic Driver In Clear Cell Renal Cell Carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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 bound VHL only 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 ZHX2 amount and nuclear localization. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated ChIP-Seq and microarray analysis showed that ZHX2 promoted NF-kB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.
|
| |
|
| Overall design |
ZHX2 is identified as a VHL substrate from a genome-wide screen, which promotes NF-kB pathway activation and ccRCC tumorigenesis. We profiled NFkB-p65 and ZHX2 occupancy genome-wide using ChIP-seq in ccRCC 786-0 cells
|
| |
|
| Contributor(s) |
Simon JM, Zhang Q |
| Citation(s) |
30026228 |
| |
| Submission date |
Jan 31, 2018 |
| Last update date |
May 10, 2023 |
| Contact name |
Jeremy Simon |
| E-mail(s) |
jsimon@ds.dfci.harvard.edu, jeremy_simon@med.unc.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Department of Data Science
|
| Street address |
450 Brookline Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA432414 |
| SRA |
SRP131906 |
Less...
More...