|
| Status |
Public on Jul 27, 2022 |
| Title |
USP13 Promotes Deubiquitination of ZHX2 and Tumorigenesis in Kidney Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Clear cell renal cell carcinoma (ccRCC) is characterized by loss of tumor suppressor Von Hippel Lindau (VHL) function. VHL is the component of E3 ligase complex that promotes the ubiquitination and degradation of hypoxia inducible factor alpha (including HIF1alpha and HIF2alpha) and Zinc Fingers And Homeoboxes 2 (ZHX2). Our recent research showed that ZHX2 contributed to ccRCC tumorigenesis in a HIF independent manner. However, it remains unknown whether ZHX2 can be regulated through deubiquitination. Here we performed a deubiquitinase (DUB) cDNA library binding screen and identified USP13 as a novel DUB that bound ZHX2 and promoted ZHX2 deubiquitination. As a result, USP13 promoted ZHX2 protein stability in an enzymatically dependent manner and depletion of USP13 led to ZHX2 downregulation in ccRCC. Functionally, USP13 depletion led to decreased cell proliferation measured by 2-D colony formation and 3-D anchorage independent growth. USP was a critical effector on maintaining kidney tumorigenesis in an orthotopic xenograft model and its depletion led to both decreased primary kidney tumorigenesis and spontaneous lung metastasis. Our results suggest that USP13 is a potential new therapeutic target in ccRCC.
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| Overall design |
RNA-seq in 786-O cells after knockdown of ZHX2 or USP13 with two different shRNAs
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| |
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| Contributor(s) |
Xie H, Zhou J, Xu Y, Liu X, Simon JM, Hepperla AJ, Liao C, Baldwin AS, Gong K, Zhang Q |
| Citation(s) |
36037364 |
| |
| Submission date |
Oct 27, 2021 |
| Last update date |
Sep 05, 2022 |
| Contact name |
Austin J Hepperla |
| E-mail(s) |
hepperla@unc.edu
|
| Organization name |
University of North Carolina at Chapel Hill
|
| Department |
Genetics
|
| Street address |
7018B Mary Ellen Jones Building
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (18)
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| Relations |
| BioProject |
PRJNA775640 |
| SRA |
SRP343502 |
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