Proapoptotic BAX and BAK control multiple initiator caspases. Academic Article uri icon

Overview

abstract

  • BAX and BAK operate at both the mitochondria and endoplasmic reticulum (ER) to regulate the intrinsic apoptotic pathway. An unresolved issue is whether any caspases can be activated in response to intrinsic apoptotic signals in the absence of BAX and BAK. Following organelle-specific intrinsic stress signals, including DNA damage and ER stress, we detected no activation of CARD-containing caspases (initiator CASP)-1, -2, -9, -11 and -12 in Bax(-/-)Bak(-/-) doubly deficient (DKO) cells. BCL-2 overexpression in these DKO cells provided no further protection to their already strong protection from DNA damage and ER stress. Moreover, there was no activation of effector CASP-3 and -7 in DKO cells, consistent with the lack of initiator caspase activity and disfavouring a BAX, BAK-independent intrinsic apoptotic pathway to activate initiator caspases. Thus, BAX and BAK confer an essential gateway for the activation of caspases in the intrinsic apoptotic pathway.

publication date

  • April 1, 2005

Research

keywords

  • Apoptosis
  • Caspases
  • DNA Damage
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2

Identity

PubMed Central ID

  • PMC1299285

Scopus Document Identifier

  • 17644371025

Digital Object Identifier (DOI)

  • 10.1038/sj.embor.7400375

PubMed ID

  • 15776018

Additional Document Info

volume

  • 6

issue

  • 4