Faculty Collaboration Database

Identification of a conserved anti-apoptotic protein that modulates the mitochondrial apoptosis pathway. PLoS One 2011;6(9):e25284

Date

10/08/2011

Pubmed ID

21980415

Pubmed Central ID

PMC3184134

DOI

10.1371/journal.pone.0025284

Scopus ID

2-s2.0-80053607442 (requires institutional sign-in at Scopus site)   25 Citations

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.

Author List

Zhang Y, Johansson E, Miller ML, Jänicke RU, Ferguson DJ, Plas D, Meller J, Anderson MW

MESH terms used to index this publication - Major topics in bold

Apoptosis
Apoptosis Regulatory Proteins
Blotting, Western
Caspase 10
Caspase 3
Caspase 8
Caspase 9
Cell Line, Tumor
Etoposide
Humans
Mitochondria
Nuclear Proteins
Proteins
RNA, Small Interfering
Staurosporine