GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE109953 Query DataSets for GSE109953
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
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)
GSM2974458 NFkB-p65_ChIP_Rep1
GSM2974459 NFkB-p65_input_Rep1
GSM2974460 ZHX2_ChIP_Rep1
BioProject PRJNA432414
SRA SRP131906

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE109953_RAW.tar 6.7 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap