Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2013 Jun 21;288(25):18184-93. doi: 10.1074/jbc.M113.466540. Epub 2013 Apr 15.

IκB kinase β (IKKβ) inhibits p63 isoform γ (TAp63γ) transcriptional activity.

Author information

1
Department of Biochemistry and Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.

Abstract

Previously, we reported that IκB kinase-β(IKKβ) phosphorylates and stabilizes TAp63γ. However, the effect of this phosphorylation on TAp63γ transcriptional activity remains unclear. In this study, we showed that overexpression of IKKβ, but not its kinase dead mutant and IKKα, can surprisingly inhibit TAp63γ transcriptional activity as measured by luciferase assays and real-time PCR analyses of p63 target genes. This inhibition was impaired by ACHP, an IKKβ inhibitor, and enhanced by TNFα that activates IKKβ. Consistently, IKKβ inhibited the binding between TAp63γ and p300, a co-activator of TAp63γ, and consequently counteracted the positive effect of p300 on TAp63γ transcriptional activity. Through phosphorylation site prediction and mass spectrometry, we identified that Ser-4 and Ser-12 of p63 are IKKβ-targeting residues. As expected, IKKβ fails to suppress the transcriptional activity of the S4A/S12A double mutant p63. These results indicate that IKKβ can suppress TAp63γ activity by interfering with the interaction between TAp63γ and p300.

KEYWORDS:

IκB kinase-β; Senescence; Signal transduction; Transcription; Tumor Necrosis Factor (TNF); p300; p63

PMID:
23589370
PMCID:
PMC3689961
DOI:
10.1074/jbc.M113.466540
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center