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

K Schumm, S Rocha, Jorge Caamano, ND Perkins

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

The p52/p100 nuclear factor kappa B (NF-kappaB) subunit (NF-kappaB2) 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, Gadd45alpha 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.
Original languageEnglish
Pages (from-to)4820-4832
Number of pages13
JournalThe EMBO journal
Volume25
Issue number20
DOIs
Publication statusPublished - 21 Sept 2006

Keywords

  • p53
  • NF-kappa B2
  • apoptosis
  • cell cycle
  • p21(WAF1)

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