The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome

J Biol Chem. 2000 Feb 18;275(7):4613-7. doi: 10.1074/jbc.275.7.4613.

Abstract

The BAG-1 protein modulates the chaperone activity of Hsc70 and Hsp70 in the mammalian cytosol and nucleus. Remarkably, BAG-1 possesses a ubiquitin-like domain at its amino terminus, suggesting a link to the ubiquitin/proteasome system. Here we show that BAG-1 is indeed associated with the 26 S proteasome in HeLa cells. Binding of the chaperone cofactor to the proteolytic complex is regulated by ATP hydrolysis and is not mediated by Hsc70 and Hsp70. The presented findings reveal a role of BAG-1 as a physical link between the Hsc70/Hsp70 chaperone system and the proteasome. In fact, targeting of BAG-1 to the proteasome promotes an association of the chaperones with the proteolytic complex in vitro and in vivo. A regulatory function of the chaperone cofactor at the interface between protein folding and protein degradation is thus indicated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cysteine Endopeptidases / metabolism*
  • DNA-Binding Proteins
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Multienzyme Complexes / metabolism*
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Transcription Factors
  • Ubiquitins / metabolism*

Substances

  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Multienzyme Complexes
  • Protein Isoforms
  • Transcription Factors
  • Ubiquitins
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex