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Proapoptotic BAX and BAK control multiple initiator caspases
Author(s) -
RuizVela Antonio,
Opferman Joseph T,
Cheng Emily HY,
Korsmeyer Stanley J
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400375
Subject(s) - microbiology and biotechnology , caspase , endoplasmic reticulum , intrinsic apoptosis , apoptosis , mitochondrion , unfolded protein response , chemistry , biology , programmed cell death , biochemistry
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.