Biological activities of HAP46/BAG-1. The HAP46/BAG-1 protein: regulator of HSP70 chaperones, DNA-binding protein and stimulator of transcription

EMBO Rep. 2004 Feb;5(2):148-53. doi: 10.1038/sj.embor.7400083.

Abstract

HAP46/BAG-1M and its isoforms affect the protein-folding activities of mammalian HSP70 chaperones. They interact with the ATP-binding domain of HSP70 or HSC70, leaving the substrate-binding site available for further interactions. Trimeric complexes can therefore form with, for example, transcription factors. Moreover, HAP46/BAG-1M and the larger isoform HAP50/BAG-1L bind to DNA non-specifically and enhance transcription in vitro and upon overexpression in intact cells. These factors are linked to positive effects on cell proliferation and survival. This review focuses on DNA-binding activity and transcriptional stimulation by HAP46/BAG-1M, and presents a molecular model for the underlying mechanism. It is proposed that transcription factors are recruited into complexes with HAP46/BAG-1M or HAP50/BAG-1L through HSP70/HSC70 and that response-element-bound complexes that contain HAP46/BAG-1M and/or HAP50/BAG-1L along with HSP70s target and affect the basal transcription machinery.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology
  • Cell Survival
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Neoplasms / metabolism
  • Protein Folding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Receptors, Steroid / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism
  • Up-Regulation / genetics

Substances

  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • HSP70 Heat-Shock Proteins
  • Protein Isoforms
  • Receptors, Steroid
  • Transcription Factors
  • Ubiquitin