Interaction of pro-apoptotic protein HGTD-P with heat shock protein 90 is required for induction of mitochondrial apoptotic cascades.
HGTD-P is a hypoxia-responsive pro-apoptotic protein that transmits hypoxic signals directly to mitochondria. When overexpressed, HGTD-P induces cell death via typical mitochondrial apoptotic cascades. However, much is unknown about post-transcriptional modification and signaling networks of HGTD-P in association with cell death-regulating proteins. We performed yeast two-hybrid screening to identify the molecules involved in HGTD-P-mediated cell death pathways. In this study, we show that heat shock protein 90 physically interacts with HGTD-P and that suppression of Hsp90 activity by low concentrations of geldanamycin reduced HGTD-P-induced mitochondrial catastrophe through inhibition of mitochondrial translocation of HGTD-P.
Kim
Jee-Youn
JY
Department of Pathology, Medical Research Center for Bioreaction to Reactive Oxygen Species, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Kim
Su-Mi
SM
Ko
Jeong-Hun
JH
Yim
Ji-Hye
JH
Park
Jin-Hae
JH
Park
Jae-Hoon
JH
D017209:Apoptosis; D016227:Benzoquinones; D002478:Cells, Cultured; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D047029:Lactams, Macrocyclic; D008565:Membrane Proteins; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D025941:Protein Interaction Mapping; D021381:Protein Transport; D011809:Quinones / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
D016227:Benzoquinones; C486647:FAM162A protein, human; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011809:Quinones; D046988:Proteasome Endopeptidase Complex; C001277:geldanamycin