title: A member of the ETS family, EHF, and the ATPase RUVBL1 inhibit p53-mediated apoptosis.
abstract: Tumour cells are known to be dependent on, or 'addicted to', not only oncogenes, but also some non-oncogenes. However, the mechanisms by which tumour cells are addicted to these genes have not been fully explained. Here, we show that overexpression of a member of the ETS family, EHF, is required for the survival of colon tumour cells that contain wild-type p53. We found that EHF directly activates the transcription of RUVBL1, an ATPase associated with chromatin-remodelling complexes. RUVBL1 blocks p53-mediated apoptosis by repressing the expression of p53 and its target genes. Moreover, we found that RUVBL1 represses p53 transcription by binding to the p53 promoter, interfering with RNF20/hBRE1-mediated histone H2B monoubiquitination and promoting PAF1-mediated histone H3K9 trimethylation. These results indicate that EHF-mediated RUVBL1 expression allows colon tumour cells to avoid p53-mediated apoptosis. Thus, EHF and RUVBL1 might be promising molecular targets for the treatment of colon tumours.
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Kenzui
authors: K
authors: Taniue
authors: Takeaki
authors: T
authors: Oda
authors: Tomoatsu
authors: T
authors: Hayashi
authors: Masumi
authors: M
authors: Okuno
authors: Tetsu
authors: T
authors: Akiyama
references: Nucleic Acids Res. 2010 Jan;38(2):382-90
references: 19906718
references: Cancer Res. 2008 May 1;68(9):3081-6; discussion 3086
references: 18451131
references: Nat Cell Biol. 2008 Apr;10(4):483-8
references: 18344985
references: Biochem Biophys Res Commun. 1999 Oct 14;264(1):119-26
references: 10527851
references: Trends Biochem Sci. 1998 Jun;23(6):213-6
references: 9644975
references: Genes Dev. 2008 Oct 1;22(19):2664-76
references: 18832071
references: Cell. 2006 May 19;125(4):703-17
references: 16713563
references: Genes Dev. 2001 Dec 15;15(24):3243-8
references: 11751630
references: Nature. 2007 Feb 8;445(7128):656-60
references: 17251933
references: Genes Dev. 2001 Dec 15;15(24):3249-62
references: 11751631
references: J Clin Oncol. 1999 Sep;17(9):2639-48
references: 10561337
references: Nat Rev Mol Cell Biol. 2001 Nov;2(11):827-37
references: 11715049
references: Nat Rev Cancer. 2004 Dec;4(12):956-65
references: 15573117
references: Mol Cell. 2009 Jun 12;34(5):521-33
references: 19524533
references: Nat Rev Cancer. 2009 Oct;9(10):714-23
references: 19730431
references: Cancer Res. 2008 Sep 1;68(17):6873-6
references: 18757398
references: Nature. 2008 Jul 10;454(7201):226-31
references: 18568025
references: Cell Stem Cell. 2009 May 8;4(5):403-15
references: 19345177
references: Cancer Res. 2008 May 1;68(9):3077-80; discussion 3080
references: 18451130
references: Science. 1998 Nov 20;282(5393):1497-501
references: 9822382
references: Trends Cell Biol. 2007 Apr;17(4):187-92
references: 17320397
references: EMBO Rep. 2009 Dec;10(12):1355-62
references: 19893577
references: Eur J Cancer. 2005 Nov;41(16):2462-78
references: 16213704
references: Mol Cell Biol. 2005 Jun;25(12):5052-60
references: 15923622