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Activated p53 induces NF-kappaB DNA binding but suppresses its transcriptional activation.

Abstract：

:NF-kappaB plays an important role in oncogenesis. Recently, we have demonstrated that loss of p53 function enhances DNA binding and transcriptional activities of NF-kappaB via IKKalpha and IKKbeta, and that glycolysis, activated by NF-kappaB, has an integral role in oncogene-induced cell transformation. Here, we show that ectopically expressed p53 induces acetylation and phosphorylation at Ser 536 of p65, an NF-kappaB component, and enhances DNA-binding activity of NF-kappaB. However, activated p53 suppresses transcriptional activity of NF-kappaB. Under non-stimulating conditions, p65 formed a complex with IKKalpha and IKKbeta. Activated p53 bound to p65 on DNA and disrupted binding of p65 to IKKbeta. Moreover, histone H3 kinase activity, which requires transcriptional activation of NF-kappaB, was diminished by p53. Thus, activated p53 may suppress transcriptional activity of NF-kappaB through inhibition of IKK and histone H3 kinase on DNA, suggesting a novel p53-mediated suppression system for tumorigenesis.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kawauchi K,Araki K,Tobiume K,Tanaka N

doi

10.1016/j.bbrc.2008.05.021

subject

Has Abstract

pub_date

2008-07-18 00:00:00

pages

137-41

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(08)00885-1

journal_volume

372

pub_type

杂志文章

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