Interaction of pro-apoptotic protein HGTD-P with heat shock protein 90 is required for induction of mitochondrial apoptotic cascades

• Published in: FEBS letters 2006-05, Vol.580 (13), p.3270-3275
• Main Authors: Kim, Jee-Youn, Kim, Su-Mi, Ko, Jeong-Hun, Yim, Ji-Hye, Park, Jin-Hae, Park, Jae-Hoon
• Format: Article
• Language: English
• Subjects: 17-(Allylamino)-17-demethoxygeldanamycin; 17-AAG; 4′,6′-diamidino-2-phenylindole; 90-kDa heat shock protein; Apoptosis; Benzoquinones; Cells, Cultured; DAPI; geldanamycin; heat shock protein; HGTD-P; HIF-1α; Hsp; HSP90 Heat-Shock Proteins - analysis; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - metabolism; Humans; hypoxia-inducible factor-1α; Lactams, Macrocyclic; Membrane Proteins; Mitochondria; Mitochondria - chemistry; Mitochondria - metabolism; mitochondrial membrane potential; Mitochondrial Proteins - analysis; Mitochondrial Proteins - metabolism; MMP; Proteasome Endopeptidase Complex - drug effects; Proteasome Endopeptidase Complex - metabolism; Protein Interaction Mapping; Protein Transport; Quinones - pharmacology; Two-Hybrid System Techniques
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.05.001

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.