Open AccessInhibition of Reaper-induced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs)
Author(s) -
Domagoj Vucic,
William J. Kaiser,
Alex J. Harvey,
Lois K. Miller
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.19.10183
Subject(s) - apoptosis , inhibitor of apoptosis , inhibitor of apoptosis domain , caspase , microbiology and biotechnology , xiap , biology , in vivo , caspase 3 , programmed cell death , biochemistry , genetics
IAPs comprise a family of inhibitors of apoptosis found in viruses and animals.In vivo binding studies demonstrated that both baculovirus andDrosophila IAPs physically interact with an apoptosis-inducing protein ofDrosophila , Reaper (RPR), through their baculovirus IAP repeat (BIR) region. Expression of IAPs blocked RPR-induced apoptosis and resulted in the accumulation of RPR in punctate perinuclear locations which coincided with IAP localization. When expressed alone, RPR rapidly disappeared from the cells undergoing RPR-induced apoptosis. Expression of P35, a caspase inhibitor, also blocked RPR-induced apoptosis and delayed RPR decline, but RPR remained cytoplasmic in its location. Mutational analysis of RPR demonstrated that caspases were not directly responsible for RPR disappearance. The physical interaction of IAPs with RPR provides a molecular mechanism for IAP inhibition of RPR’s apoptotic activity.