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J Cell Biol. 2013 Apr 29;201(3):427-37. doi: 10.1083/jcb.201205064.

Deacetylation of p53 induces autophagy by suppressing Bmf expression.

Author information

1
Chronic Obstructive Pulmonary Disease Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.

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.

PMID:
23629966
PMCID:
PMC3639396
DOI:
10.1083/jcb.201205064
[Indexed for MEDLINE]
Free PMC Article

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