Deacetylation of p53 induces autophagy by suppressing Bmf expression. Academic Article uri icon

Overview

MeSH

  • Acetylation
  • Animals
  • Butyric Acid
  • Cell Nucleus
  • Cells, Cultured
  • Epithelial Cells
  • Gene Silencing
  • Histone Deacetylase 1
  • Histone Deacetylase Inhibitors
  • Humans
  • Hydroxamic Acids
  • Interferon-gamma
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Respiratory Mucosa

MeSH Major

  • Adaptor Proteins, Signal Transducing
  • Autophagy
  • Gene Expression
  • Protein Processing, Post-Translational
  • Tumor Suppressor Protein p53

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.

publication date

  • April 29, 2013

has subject area

  • Acetylation
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Autophagy
  • Butyric Acid
  • Cell Nucleus
  • Cells, Cultured
  • Epithelial Cells
  • Gene Expression
  • Gene Silencing
  • Histone Deacetylase 1
  • Histone Deacetylase Inhibitors
  • Humans
  • Hydroxamic Acids
  • Interferon-gamma
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational
  • Respiratory Mucosa
  • Tumor Suppressor Protein p53

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3639396

Digital Object Identifier (DOI)

  • 10.1083/jcb.201205064

PubMed ID

  • 23629966

Additional Document Info

start page

  • 427

end page

  • 437

volume

  • 201

number

  • 3