4O1V

SPOP Promotes Tumorigenesis by Acting as a Key Regulatory Hub in Kidney Cancer

4O1V の概要

• エントリーDOI: 10.2210/pdb4o1v/pdb
• 分子名称: Speckle-type POZ protein, Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (3 entities in total)
• 機能のキーワード: ubl conjugation pathway, ligase, ubiquitin, e3, spop, math, pten, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: O43791; Cytoplasm: P60484
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18019.44

構造登録者

Calabrese, M.F.,Watson, E.R.,Schulman, B.A. (登録日: 2013-12-16, 公開日: 2014-04-30, 最終更新日: 2023-09-20)

主引用文献

Li, G.,Ci, W.,Karmakar, S.,Chen, K.,Dhar, R.,Fan, Z.,Guo, Z.,Zhang, J.,Ke, Y.,Wang, L.,Zhuang, M.,Hu, S.,Li, X.,Zhou, L.,Li, X.,Calabrese, M.F.,Watson, E.R.,Prasad, S.M.,Rinker-Schaeffer, C.,Eggener, S.E.,Stricker, T.,Tian, Y.,Schulman, B.A.,Liu, J.,White, K.P.
SPOP Promotes Tumorigenesis by Acting as a Key Regulatory Hub in Kidney Cancer.
Cancer Cell, 25:455-468, 2014

PubMed Abstract: Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP, which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and apoptosis, including the tumor suppressor PTEN, ERK phosphatases, the proapoptotic molecule Daxx, and the Hedgehog pathway transcription factor Gli2. Knockdown of SPOP specifically kills ccRCC cells, indicating that it may be a promising therapeutic target. Collectively, our results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis.

PubMed: 24656772
DOI: 10.1016/j.ccr.2014.02.007

実験手法

X-RAY DIFFRACTION (2 Å)