Regulation of the heat shock conjugate Hsc70 in the mammalian cell: the characterization of the anti-apoptotic protein BAG-1 provides novel insights

Biol Chem. 1998 Mar;379(3):269-74.

Abstract

The regulation of the chaperone activity of the heat shock cognate Hsc70 protein in the mammalian cell involves a cooperation with chaperone cofactors such as Hsp40, the Hsp70-interacting protein Hip, and the Hsc70/Hsp90-organizing protein Hop. Recent studies have now added another component to the list of Hsc70 cofactors, the BAG-1 protein. Initially identified as an anti-apoptotic molecule and binding partner of the cell death inhibitor Bcl-2, BAG-1 appears to fulfill its cellular function through a modulation of Hsc70's chaperone activity. BAG-1 acts as a nucleotide exchange factor in the Hsc70 ATPase cycle, thereby competing with the cofactor Hip which stabilizes the ADP-bound state of Hsc70. The functional characterization of BAG-1 thus reveals an unexpected versatility in the regulation of Hsc70 and appears to provide a link between apoptosis and the cellular chaperone machinery.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins*
  • Mammals
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Transcription Factors
  • Ubiquitins / chemistry
  • Ubiquitins / metabolism

Substances

  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Transcription Factors
  • Ubiquitins
  • Adenosine Triphosphatases