Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative regulator of HIF-1, through binding to pro-survival Bcl-2 family proteins.

ABSTRACT: Inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS) is a dominant negative transcription factor that represses hypoxia-inducible factor 1 (HIF-1) activity. In this study, we show that IPAS also functions as a pro-apoptotic protein through binding to pro-survival Bcl-2 family members. In a previous paper, we reported that NF-κB-dependent IPAS induction by cobalt chloride repressed the hypoxic response in PC12 cells. We found that prolonged incubation under the same conditions caused apoptosis in PC12 cells. Repression of IPAS induction protected cells from apoptosis. Furthermore, knockdown of IPAS recovered cell viability. EGFP-IPAS protein was localized in both the nucleus and the cytoplasm, with a large fraction associated with mitochondria. Mitochondrial IPAS induced mitochondria depolar

SUBMITTER: Torii S 

PROVIDER: S-EPMC3190112 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature