부산대학교 도서관

Interferon [gamma], (IFN-[gamma])-induced cell death is mediated by the BH3-only domain protein, Bik, in a p53-independent manner. However, the effect of IFN-[gamma] on p53 and how this affects autophagy have not been reported. The present study demonstrates that IFN-[gamma] down-regulated expression of the BH3 domain-only protein, Bmf, in human and mouse airway epithelial cells in a p53-dependent manner. p53 also suppressed Bmf expression in response to other cell death--stimulating agents, including ultraviolet radiation and histone deacetylase inhibitors. IFN-[gamma] did not affect Bmf messenger RNA half-life but increased nuclear p53 levels and the interaction of p53 with the Bmf promoter. IFN-[gamma]-induced interaction of HDAC1 and p53 resulted in the deacetylation of p53 and suppression of Bmf expression independent of p53's proline-rich domain. Suppression of Bmf facilitated IFN-[gamma]-induced autophagy by reducing the interaction of Beclin-1 and Bcl-2. Furthermore, autophagy was prominent in cultured [bmf.sup.-/-] but not in [bmf.sup.+/+] cells. Collectively, these observations show that deacetylation of p53 suppresses Bmf expression and facilitates autophagy. www.jcb.org/cgi/doi/10.1083/job.201205064