BRD7 is candidate tumour suppressor gene required for p53 frunction (Nat Cell Biol, 2010, 12:380-389)

報告日期: 2011/04/15
報告時間: 15:10/16:00
報告學生: 王韋然
講評老師: 洪良宜

Full Text:

BRD7 is a candidate tumour suppressor gene required for p53 function
Jarno Drost, Fiamma Mantovani, Francesca Tocco, Ran Elkon, Anna Comel, Henne Holstege, Ron Kerkhoven, Jos Jonkers, P. Mathijs Voorhoeve, Reuven Agamiand Giannino Del Sal
Nature cell biology 2010 April; 12:380-389
Speaker : 王韋然
Commentator : 洪良宜 老師
Date: 2011/04/15 15:10-16:00
Location: Room 602
Oncogene-induced senescence (OIS) is a cellular response that may be reflected for protection against tumor development. The transcription factor p53 is a well-known tumor suppressor. In OIS, the p53 mutants and dysfunctional p53 pathway could provide an advantage for promoting cell proliferate and leading to tumorigenesis. However, for many wild-type p53 tumors, the genetic alterations leading to functional impairment of the tumour suppressive responsive are not identified. In this study, a genetic screen, GFP-growth competition assay of BJ/ET/p14ARF-KD/Rasv12ER, was performed to identify the novel targets for dissecting the link between OIS and tumorgenesis. BRD7 was identified as a component of a BRG1-specific SWI/SNF (switch/sucrose non-fermentable) chromatin-remodeling complex. The authors demonstrated that BRD7 can benefit to inhibit cell growth and promote cell senescence. Rasv12 oncogene activation stimulates BRD7 to interact with p53. Meanwhile, the cluster of genes, including p21 and HMD2, regulated by the p53/BRD7 complex was clarified by a systemic approach. Furthermore, the p53/BRD73 complex can further recruit p300, an acetyltransferase, and enhance the acetylations of p53 and histone. Taken together, this study suggests that BRD7 suppresses tumorigenicity by serving as a p53 cofactor required for the efficient induction of p53-dependent OIS.
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