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Gene information | Literature | Expression | lncRNA | Mutation | Homolog

Basic Information

Gene ID

5036

Name

PA2G4

Synonymous

proliferation-associated 2G4, 38kDa;PA2G4;proliferation-associated 2G4, 38kDa

Definition

ErbB-3 binding protein 1|ErbB3-binding protein Ebp1|cell cycle protein p38-2G4 homolog|erbB3-binding protein 1|proliferation-associated 2G4, 38kD|proliferation-associated protein 2G4

Position

12q13.2

Gene type

protein-coding

Title

Abstract

Negative regulation of p53 by the long isoform of ErbB3 binding protein Ebp1 in brain tumors.

The ErbB3 binding protein Ebp1 has been implicated in a number of human cancers. Ebp1 includes 2 isoforms, p48 and p42, that exhibit different cellular activities. Here we show that the larger p48 isoform is transforming and that it promotes cell growth, clonogenicity, and invasion in human glioblastoma (GBM). P48 overexpression in GBM cells facilitated tumorigenesis and enhanced tumor growth in mouse xenograft models. Human GBM tissues displayed elevated levels of p48 compared with surrounding normal tissues or low-grade tumors. Notably, p48 levels were inversely correlated with poor prognosis in GBM patients. We determined that p48 binds to the p53 E3 ligase HDM2, enhancing HDM2-p53 association and thereby promoting p53 polyubiquitination and degradation to reduce steady-state p53 levels and activity. Together, our findings suggest that p48 functions as an oncogene by promoting glioma tumorigenicity via interactions with HDM2 that contribute to p53 downregulation.