title: Deacetylation of p53 induces autophagy by suppressing Bmf expression.
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.
authors: Chronic Obstructive Pulmonary Disease Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors: Amelia U
authors: AU
authors: Contreras
authors: Yohannes
authors: Y
authors: Mebratu
authors: Monica
authors: M
authors: Delgado
authors: Gilbert
authors: G
authors: Montano
authors: Chien-An A
authors: CA
authors: Hu
authors: Stefan W
authors: SW
authors: Ryter
authors: Augustine M K
authors: AM
authors: Choi
authors: Yuting
authors: Y
authors: Lin
authors: Jialing
authors: J
authors: Xiang
authors: Hitendra
authors: H
authors: Chand
authors: Yohannes
authors: Y
authors: Tesfaigzi
mesh_terms: D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D020148:Butyric Acid / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells; D015870:Gene Expression; D020868:Gene Silencing; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D020545:Respiratory Mucosa; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C435486:Bmf protein, mouse; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D016159:Tumor Suppressor Protein p53; D020148:Butyric Acid; C012589:trichostatin A; D007371:Interferon-gamma; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1
references: J Biol Chem. 2003 Sep 26;278(39):37439-50
references: 12876282
references: J Clin Invest. 2000 Jul;106(1):25-35
references: 10880045
references: PLoS One. 2011;6(9):e24705
references: 21931823
references: J Immunol. 2007 Jun 15;178(12):8107-16
references: 17548649
references: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3787-92
references: 17360431
references: Nat Cell Biol. 2000 Sep;2(9):563-8
references: 10980695
references: Science. 2001 Jun 8;292(5523):1910-5
references: 11397945
references: Immunity. 2009 Oct 16;31(4):539-50
references: 19833085
references: Nature. 2000 Nov 16;408(6810):377-81
references: 11099047
references: Mol Cell. 2012 Aug 10;47(3):359-70
references: 22742832
references: Mol Cell Biol. 2004 Feb;24(4):1570-81
references: 14749373
references: Cancer Res. 2000 Oct 15;60(20):5673-80
references: 11059759
references: Am J Physiol Lung Cell Mol Physiol. 2002 Dec;283(6):L1315-21
references: 12388377
references: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14559-63
references: 8962091
references: Genes Dev. 1995 Jan 1;9(1):15-30
references: 7828849
references: Mol Cell. 2006 Dec 28;24(6):827-39
references: 17189186
references: Nat Med. 1998 Jul;4(7):835-8
references: 9662377
references: J Immunol. 2002 May 1;168(9):4764-71
references: 11971027
references: Nucleic Acids Res. 2009 May;37(8):2688-98
references: 19273532
references: Oncogene. 2005 Jan 20;24(4):605-15
references: 15580300
references: Genes Dev. 1999 Oct 1;13(19):2490-501
references: 10521394
references: J Cell Biol. 2002 Apr 29;157(3):455-68
references: 11980920
references: Mol Cell Biol. 2003 Dec;23(23):8846-61
references: 14612423
references: Cell. 2008 May 16;133(4):612-26
references: 18485870
references: Oncogene. 2008 Mar 6;27(11):1562-71
references: 17873905
references: J Cell Biol. 2008 Nov 3;183(3):429-39
references: 18981230
references: Genes Dev. 2007 Mar 15;21(6):627-31
references: 17369394
references: Cancer Cell. 2006 Apr;9(4):273-85
references: 16616333
references: Cancer Res. 2011 Jun 1;71(11):3763-71
references: 21512142
references: Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1925-30
references: 21245319
references: Cell Death Differ. 2010 Nov;17(11):1672-83
references: 20706276
references: Cell Death Differ. 2010 Feb;17(2):255-67
references: 19927155
references: Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1102-9
references: 18390829
references: Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2259-64
references: 14982997
references: J Biol Chem. 1999 Oct 15;274(42):29677-82
references: 10514438
references: Nat Rev Immunol. 2005 Mar;5(3):189-200
references: 15719025
references: J Biol Chem. 2009 Feb 20;284(8):5158-64
references: 19106109
references: Cell Death Differ. 2010 Jan;17(1):86-92
references: 19543236
references: Nat Cell Biol. 2008 Jun;10(6):676-87
references: 18454141
references: Am J Respir Cell Mol Biol. 2006 May;34(5):537-47
references: 16439804
references: Science. 2001 Sep 7;293(5536):1829-32
references: 11546872
references: J Biol Chem. 1997 Jun 27;272(26):16351-7
references: 9195941
references: Cell Death Differ. 2010 Apr;17(4):699-709
references: 19851330
references: Cell. 1997 Aug 22;90(4):595-606
references: 9288740
references: J Exp Med. 2008 Mar 17;205(3):641-55
references: 18299399
references: Apoptosis. 2006 Aug;11(8):1349-57
references: 16830229
references: Mol Cell. 2011 Apr 8;42(1):23-35
references: 21353614
references: Nature. 1972 Nov 10;240(5376):102-4
references: 4564814
references: Mol Cell Biol. 2007 Feb;27(4):1425-32
references: 17158931
references: Cell. 2006 Jan 13;124(1):207-19
references: 16413492
references: Curr Opin Cell Biol. 2010 Apr;22(2):181-5
references: 20044243
references: Nat Rev Drug Discov. 2007 Dec;6(12):975-90
references: 18049472
references: Mol Cell. 2004 Dec 3;16(5):725-36
references: 15574328
references: J Biol Chem. 2000 Apr 14;275(15):11327-32
references: 10753945
references: Cell Death Differ. 2006 Jan;13(1):129-40
references: 15947789
references: Cancer Res. 2011 Jun 15;71(12):4247-59
references: 21512143
references: J Immunol. 2002 Nov 15;169(10):5919-25
references: 12421976
references: J Biol Chem. 2011 Jul 29;286(30):26533-40
references: 21673109