Prevention of apoptosis by the interaction between FIH1 and Bax.
Bax induces mitochondrial-dependent cell apoptosis signals in mammalian cells. However, the mechanism of how Bax is kept inactive is not fully elucidated. Here, we identify FIH1 as a potential interactor of Bax through mass spectrometry analysis. Coimmunoprecipitation and GST pull-down experiments show that FIH1 can directly interact with Bax. Bax-mediated apoptosis is suppressed by FIH1 overexpression, but accelerated by FIH1 deficiency. FIH1 functions as a cytosol retention factor of Bax, blocking Bax translocation from cytosol to mitochondria in response to apoptotic stimuli. Overall, there results unveil a novel role of FIH1 in the regulation of Bax-mediated apoptosis.
Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Tongji University, Shanghai, China. yanbiao1982@hotmail.com
Biao
B
Yan
Men
M
Kong
Yi-han
YH
Chen
D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000378:metabolism; D006899:Mixed Function Oxygenases; D010100:Oxygen / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D021241:Spectrometry, Mass, Electrospray Ionization; D019311:Staurosporine / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D051028:bcl-2-Associated X Protein; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D019311:Staurosporine; D010100:Oxygen