BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Apoptosis Regulatory Proteins
  • BH3 Interacting Domain Death Agonist Protein
  • Membrane Proteins
  • Neurons
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein

abstract

  • Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled. We provide in vivo evidence demonstrating an essential role of the proteins BID, BIM, and PUMA in activating BAX and BAK. Bid, Bim, and Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas. Genetic deletion of Bid, Bim, and Puma prevented the homo-oligomerization of BAX and BAK, and thereby cytochrome c-mediated activation of caspases in response to diverse death signals in neurons and T lymphocytes, despite the presence of other BH3-only molecules. Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA family of proteins.

publication date

  • December 3, 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3163443

Digital Object Identifier (DOI)

  • 10.1126/science.1190217

PubMed ID

  • 21127253

Additional Document Info

start page

  • 1390

end page

  • 3

volume

  • 330

number

  • 6009