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National Institute of Environmental Health Sciences

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Publication Detail

Title: Identification of a conserved anti-apoptotic protein that modulates the mitochondrial apoptosis pathway.

Authors: Zhang, Yu; Johansson, Elisabet; Miller, Marian L; Jänicke, Reiner U; Ferguson, Donald J; Plas, David; Meller, Jarek; Anderson, Marshall W

Published In PLoS One, (2011)

Abstract: Here we identified an evolutionarily highly conserved and ubiquitously expressed protein (C9orf82) that shows structural similarities to the death effector domain of apoptosis-related proteins. RNAi knockdown of C9orf82 induced apoptosis in A-549 and MCF7/casp3-10b lung and breast carcinoma cells, respectively, but not in cells lacking caspase-3, caspase-10 or both. Apoptosis was associated with activated caspases-3, -8, -9 and -10, and inactivation of caspases 10 or 3 was sufficient to block apoptosis in this pathway. Apoptosis upon knockdown of C9orf82 was associated with increased caspase-10 expression and activation, which was required for the generation of an 11 kDa tBid fragment and activation of Caspase-9. These data suggest that C9orf82 functions as an anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop. We designate this ubiquitously expressed and evolutionarily conserved anti-apoptotic protein Conserved Anti-Apoptotic Protein (CAAP). We also demonstrated that treatment of MCF7/casp3-10b cells with staurosporine and etoposides induced apoptosis and knockdown of CAAP expression. This implies that the CAAP protein could be a target for chemotherapeutic agents.

PubMed ID: 21980415 Exiting the NIEHS site

MeSH Terms: Apoptosis Regulatory Proteins/genetics; Apoptosis Regulatory Proteins/metabolism*; Apoptosis/drug effects; Apoptosis/genetics; Blotting, Western; Caspase 10/genetics; Caspase 10/metabolism; Caspase 3/genetics; Caspase 3/metabolism; Caspase 8/genetics; Caspase 8/metabolism; Caspase 9/genetics; Caspase 9/metabolism; Cell Line, Tumor; Etoposide/pharmacology; Humans; Mitochondria/metabolism*; Nuclear Proteins/genetics; Nuclear Proteins/metabolism*; Proteins/genetics; Proteins/metabolism*; RNA, Small Interfering; Staurosporine/pharmacology

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