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Apoptosis inhibitor 5 is an endogenous inhibitor of caspase‐2
Author(s) -
Imre Gergely,
Berthelet Jean,
Heering Jan,
Kehrloesser Sebastian,
Melzer Inga Maria,
Lee Byung Il,
Thiede Bernd,
Dötsch Volker,
Rajalingam Krishnaraj
Publication year - 2017
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 - 10.15252/embr.201643744
Subject(s) - german , library science , center (category theory) , chemistry , philosophy , computer science , linguistics , crystallography
Caspases are key enzymes responsible for mediating apoptotic cell death. Across species, caspase‐2 is the most conserved caspase and stands out due to unique features. Apart from cell death, caspase‐2 also regulates autophagy, genomic stability and ageing. Caspase‐2 requires dimerization for its activation which is primarily accomplished by recruitment to high molecular weight protein complexes in cells. Here, we demonstrate that apoptosis inhibitor 5 ( API 5/ AAC 11) is an endogenous and direct inhibitor of caspase‐2. API 5 protein directly binds to the caspase recruitment domain ( CARD ) of caspase‐2 and impedes dimerization and activation of caspase‐2. Interestingly, recombinant API 5 directly inhibits full length but not processed caspase‐2. Depletion of endogenous API 5 leads to an increase in caspase‐2 dimerization and activation. Consistently, loss of API 5 sensitizes cells to caspase‐2‐dependent apoptotic cell death. These results establish API 5/ AAC ‐11 as a direct inhibitor of caspase‐2 and shed further light onto mechanisms driving the activation of this poorly understood caspase.