Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity

Cell. 1995 Jan 27;80(2):279-84. doi: 10.1016/0092-8674(95)90410-7.

Abstract

Using a protein interaction cloning technique, we identified cDNAs that encode a novel Bcl-2-binding protein, termed BAG-1. The BAG-1 protein shares no significant homology with Bcl-2 or other Bcl-2 family proteins, which can form homo- and heterodimers. In gene transfer experiments using a human lymphoid cell line, Jurkat, coexpression of BAG-1 and Bcl-2 provided markedly increased protection from cell death induced by several stimuli, including staurosporine, anti-Fas antibody, and cytolytic T cells, relative to cells that contained gene transfer-mediated elevations in either BAG-1 or Bcl-2 protein alone. BAG-transfected 3T3 fibroblasts also exhibited prolonged cell survival in response to an apoptotic stimulus. The findings indicate that bag-1 represents a new type of anti-cell death gene and suggest that some routes of apoptosis induction previously ascribed to Bcl-2-independent pathways may instead reflect a need for the combination of Bcl-2 and BAG-1.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Alkaloids / pharmacology
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / blood
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Death / physiology*
  • Cell Line
  • Cell Survival / drug effects
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Gene Library
  • Humans
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2
  • Radiation-Sensitizing Agents / pharmacology
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / isolation & purification
  • Staurosporine
  • Substrate Specificity
  • Transcription Factors
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Radiation-Sensitizing Agents
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Staurosporine

Associated data

  • GENBANK/U17162