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Mst3, a Novel Mitochondrial Protein Kinase, Regulates Proapoptotic Proteins in Response to Apoptotic Stimuli
Author(s) -
Yuan ChiunJye,
Lin ChiaYing,
Wu HungYi
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a506-b
Subject(s) - apoptosis , mitochondrion , microbiology and biotechnology , staurosporine , apoptosis inducing factor , protein kinase a , biology , programmed cell death , kinase , cytochrome c , caspase , biochemistry
Mitochondria play a central role in regulating cell apoptosis. Several mitochondrial proapoptotic proteins, such as apoptotic‐inducing factor (AIF), endonuclease G (EndoG) and Smac/DIABLO, are liberated in response to death stimuli to participate in the process of apoptosis. However, the regulation of these potentially toxic mitochondrial proteins is unclear by far. Here we report that Mst3 (mammalian Ste20‐like protein kinase 3) is a novel mitochondrial serine/threonine protein kinase that induce apoptosis of HeLa and 3A‐sub‐E cells probably through the regulation of the activity of AIF and EndoG. The mitochondria residing of Mst3 was first demonstrated by the co‐localization of Mst3 and MitotrackerTM, a mitochondrial marker, cytochrome C (Cyto C), AIF and EndoG under the fluorescence microscope. This observation was further proved by the observation of electron microscope and the Western blot analysis of isolated mitochondrial fraction. Interestingly, Mst3 was shown to associate with AIF and EndoG but not Cyto C in mitochondria by co‐immunoprecipitation and pull‐down assay. Further studies showed that Mst3 accompanied with AIF and EndoG could be redistributed from mitochondria to nucleus in response to the treatment of staurosporine. These results provide a paradigm for caspase‐independent death pathway, in which Mst3 may play a crucial role in triggering the apoptosis by the regulation of the mitochondrial proapoptotic proteins. (The work was supported by National Science Council, ROC (Taiwan) under Contract No. NSC‐94‐2311‐B‐009‐003.)