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The mitochondrial ARTS protein promotes apoptosis through targeting XIAP
Author(s) -
Gottfried Yossi,
Rotem Asaf,
Lotan Rona,
Steller Hermann,
Larisch Sarit
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600155
Subject(s) - xiap , carcinogenesis , library science , medicine , apoptosis , pathology , biology , caspase , computer science , cancer , programmed cell death , genetics
ARTS is an unusual septin‐like mitochondrial protein that was originally shown to mediate TGF‐beta‐induced apoptosis. Recently, we found that ARTS is also important for cell killing by other pro‐apoptotic factors, such as arabinoside, etoposide, staurosporine and Fas. In Drosophila , the IAP antagonists Reaper, Hid and Grim are essential for the induction of virtually all apoptotic cell death. We found that mutations in peanut , which encodes a Drosophila homologue of ARTS, can dominantly suppress cell killing by Reaper, Hid and Grim, indicating that peanut acts downstream or in parallel to these. In mammalian cells, ARTS is released from mitochondria upon pro‐apoptotic stimuli and then binds to XIAP. Binding of ARTS to XIAP is direct, as recombinant ARTS and XIAP proteins can bind to each other in vitro . ARTS binding to XIAP is specific and related to its pro‐apoptotic function, as mutant forms of ARTS (or related septins) that fail to bind XIAP failed to induce apoptosis. ARTS leads to decreased XIAP protein levels and caspase activation. Our data suggest that ARTS induces apoptosis by antagonizing IAPs.