Regulation of p53 tumour suppressor target gene expression by the p52 NF-κB subunit

被引:110
作者
Schumm, Katie
Rocha, Sonia
Caamano, Jorge
Perkins, Neil D.
机构
[1] Univ Dundee, Div Gene Regulat & Express, Coll Life Sci, Dundee DD1 5EH, Scotland
[2] Univ Birmingham, Div Immun & Infect, MRC, Ctr Immune Regulat,Med Sch, Birmingham, W Midlands, England
关键词
apoptosis; cell cycle; NF-kappa B2; p53; p21(WAF1);
D O I
10.1038/sj.emboj.7601343
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The p52/p100 nuclear factor kappa B (NF-kappa B) subunit (NF-kappa B2) is aberrantly expressed in many tumour types and has been implicated as a regulator of cell proliferation. Here, we demonstrate that endogenous p52 is a direct regulator of Cyclin D1 expression. However, stimulation of Cyclin D1 expression alone cannot account for all the cell cycle effects of p52/p100 and we also find that p52 represses expression of the Cyclin-dependent kinase inhibitor p21(WAF/CIP1). Significantly, this latter effect is dependent upon basal levels of the tumour suppressor p53. By contrast, p52 cooperates with p53 to regulate other known p53 target genes such as PUMA, DR5, Gadd45 alpha and Chk1. p52 associates directly with these p53-regulated promoters where it regulates coactivator and corepressor binding. Moreover, recruitment of p52 is p53 dependent and does not require p52-DNA-binding activity. These results reveal a complex role for p52 as regulator of cell proliferation and p53 transcriptional activity. Furthermore, they imply that in some cell types, p52 can regulate p53 function and influence p53-regulated decision-making following DNA damage and oncogene activation.
引用
收藏
页码:4820 / 4832
页数:13
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