Opposing roles of the two isoforms of ErbB3 binding protein 1 in human cancer cells

Int J Cancer. 2016 Sep 15;139(6):1202-8. doi: 10.1002/ijc.30165. Epub 2016 May 17.

Abstract

The different functions of the two isoforms of ErbB3 binding protein 1 (Ebp1), p48 and p42, have recently become the focus of interest as they reveal contradictory roles in cell growth promoting ability. The conformational change that crystal structure of p42 was shown to lack α helices at the amino-terminus present in p48 represents the differential binding partners and protein modifications of two Ebp1 isoforms. N-terminal specific phosphorylation by CDK2 and deregulation of the p53 tumor suppressor through specific interaction with HDM2 and Akt activation is postulated to contribute to p48-mediated tumorigenesis. The short isoform p42 Ebp1, which is actual binding partner of ErbB3 has been implicated as a tumor suppressor with many binding partners such as Rb, HDAC2, Sin3A and the p85 subunit of PI3K with HSP70/CHIP, inhibiting its own antiproliferative activity or inhibiting PI3K activity. The aim of the current review is to provide a summary on distinctive cellular functions of two Ebp1 proteins and their molecular partners that might be responsible for the unique functions of each isoform of Ebp1.

Keywords: Ebp1; oncogene; tumor suppressor gene.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Weight
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Protein Binding
  • Protein Biosynthesis
  • Protein Isoforms
  • Protein Processing, Post-Translational
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Transcription, Genetic

Substances

  • Adaptor Proteins, Signal Transducing
  • PA2G4 protein, human
  • Protein Isoforms
  • RNA-Binding Proteins