دورية أكاديمية
VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma
| العنوان: | VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma |
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| المؤلفون: | Zhang, J., Wu, T., Simon, J., Takada, M., Saito, R., Fan, C., Liu, X.-D., Jonasch, E., Xie, L., Chen, X., Yao, X., Teh, B.T., Tan, P., Zheng, X., Li, M., Lawrence, C., Fan, J., Geng, J., Liu, X., Hu, L., Wang, J., Liao, C., Hong, K., Zurlo, G., Parker, J.S., Todd Auman, J., Perou, C.M., Kimryn Rathmell, W., Kim, W.Y., Kirschner, M.W., Kaelin, W.G., Baldwin, A.S., Zhang, Q. |
| المصدر: | Science, 361(6399) |
| بيانات النشر: | American Association for the Advancement of Science |
| سنة النشر: | 2018 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Carcinoma, Renal Cell, Homeodomain Proteins, NF-kappa B, Humans, Chromatin Immunoprecipitation, Gene Expression Regulation, Neoplastic, Animals, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Kidney Neoplasms, Hydroxylation, Molecular Targeted Therapy, Mutation, SCID, Female, Substrate Specificity, Oncogenes, Transcription Factors |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://doi.org/10.17615/qek5-1w20Test; https://cdr.lib.unc.edu/downloads/v692tg78d?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/v692tg78dTest |
| DOI: | 10.17615/qek5-1w20 |
| الإتاحة: | https://doi.org/10.17615/qek5-1w20Test https://cdr.lib.unc.edu/downloads/v692tg78d?file=thumbnailTest https://cdr.lib.unc.edu/downloads/v692tg78dTest |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.5DB75D9D |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/qek5-1w20 |
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