PDBsum entry 4o1v

Protein binding

PDB id: 4o1v

Contents

Protein chain

141 a.a.

Ligands

PRO-GLU-ALA-SER-SER-SER-THR

Waters ×105

PDB id:

4o1v

Name:

Protein binding

Title:

Spop promotes tumorigenesis by acting as a key regulatory hub in kidney cancer

Structure:

Speckle-type poz protein. Chain: a. Fragment: math domain (unp residues 28-166). Synonym: hib homolog 1, roadkill homolog 1. Engineered: yes. Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase pten. Chain: b. Fragment: unp residues 354-368.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: spop. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.00Å R-factor: 0.193 R-free: 0.221

Authors:

M.F.Calabrese,E.R.Watson,B.A.Schulman

Key ref:

G.Li et al. (2014). SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer. Cancer Cell, 25, 455-468. PubMed id: 24656772 DOI: 10.1016/j.ccr.2014.02.007

Date:

16-Dec-13 Release date: 30-Apr-14

Protein chain

O43791  (SPOP_HUMAN) -  Speckle-type POZ protein from Homo sapiens

Seq: 374 a.a.

Struc: 141 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.ccr.2014.02.007

Cancer Cell 25:455-468 (2014)

PubMed id: 24656772

SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer.

G.Li, W.Ci, S.Karmakar, K.Chen, R.Dhar, Z.Fan, Z.Guo, J.Zhang, Y.Ke, L.Wang, M.Zhuang, S.Hu, X.Li, L.Zhou, X.Li, M.F.Calabrese, E.R.Watson, S.M.Prasad, C.Rinker-Schaeffer, S.E.Eggener, T.Stricker, Y.Tian, B.A.Schulman, J.Liu, K.P.White.

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.