4O1V

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

Summary for 4O1V

• Entry DOI: 10.2210/pdb4o1v/pdb
• Descriptor: Speckle-type POZ protein, Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (3 entities in total)
• Functional Keywords: ubl conjugation pathway, ligase, ubiquitin, e3, spop, math, pten, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: O43791; Cytoplasm: P60484
• Total number of polymer chains: 2
• Total formula weight: 18019.44

Authors

Calabrese, M.F.,Watson, E.R.,Schulman, B.A. (deposition date: 2013-12-16, release date: 2014-04-30, Last modification date: 2023-09-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)