Deacetylation of p53 induces autophagy by suppressing bmf expression

Amelia U. Contreras, Yohannes Mebratu, Monica Delgado, Gilbert Montano, Chien an A. Hu, Stefan W. Ryter, Augustine M.K. Choi, Yuting Lin, Jialing Xiang, Hitendra Chand, Yohannes Tesfaigzi

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Interferon γ(IFN-γ)-induced cell death is mediated by the BH3-only domain protein, Bik, in a p53-independent manner. However, the effect of IFN-γ on p53 and how this affects autophagy have not been reported. The present study demonstrates that IFN-γ 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-γ did not affect Bmf messenger RNA half-life but increased nuclear p53 levels and the interaction of p53 with the Bmf promoter. IFN-γ-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-γ-induced autophagy by reducing the interaction of Beclin-1 and Bcl-2. Furthermore, autophagy was prominent in cultured bmf-/- but not in bmf+/+ cells. Collectively, these observations show that deacetylation of p53 suppresses Bmf expression and facilitates autophagy.

Original languageEnglish (US)
Pages (from-to)427-437
Number of pages11
JournalJournal of Cell Biology
Volume201
Issue number3
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Cell Biology

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