CREB-binding protein is a nuclear integrator of nuclear factor-kappaB and p53 signaling.

Publication/Presentation Date

1-22-1999

Abstract

Transcriptional coactivators may function as nuclear integrators by coordinating diverse signaling events. Here we show that the p65 (RelA) component of nuclear factor-kappaB (NF-kappaB) and p53 mutually repress each other's ability to activate transcription. Additionally, tumor necrosis factor-activated NF-kappaB is inhibited by UV light-induced p53. Both p65 and p53 depend upon the coactivator CREB-binding protein (CBP) for maximal activity. Increased levels of the coactivator relieve p53-mediated repression of NF-kappaB activity and p65-mediated repression of p53-dependent gene expression. Nuclear competition for limiting amounts of CBP provides a novel mechanism for altering the balance between the expression of NF-kappaB-dependent proliferation or survival genes and p53-dependent genes involved in cell cycle arrest and apoptosis.

Volume

274

Issue

4

First Page

1879

Last Page

1882

ISSN

0021-9258

Disciplines

Medicine and Health Sciences

PubMedID

9890939

Department(s)

Department of Medicine

Document Type

Article

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