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PMID: 17434128 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB.

Molecular cell ·Vol. 26 ·No. 1 ·2007-04-13 ·Pages 75-87

Huang WC, Ju TK, Hung MC, Chen CC

Abstract

CBP plays a central role in coordinating and integrating multiple signaling pathways. Competition between NF-kappaB and p53 for CBP is a crucial determinant of whether a cell proliferates or undergoes apoptosis. However, how the CBP-dependent crosstalk between these two transcription factors is regulated remains unclear. Here, we show that IKKalpha phosphorylates CBP at serine 1382 and serine 1386 and consequently increases CBP's HAT and transcriptional activities. Importantly, such phosphorylation enhances NF-kappaB-mediated gene expression and suppresses p53-mediated gene expression by switching the binding preference of CBP from p53 to NF-kappaB, thus promoting cell growth. The CBP phosphorylation also correlates with constitutive IKKalpha activation in human lung tumor tissue compared with matched nontumor lung tissue. Our results suggest that phosphorylation of CBP by IKKalpha regulates the CBP-mediated crosstalk between NF-kappaB and p53 and thus may be a critical factor in the promotion of cell proliferation and tumor growth.

MeSH Terms
Amino Acid Sequence CREB-Binding Protein/metabolism Cell Line Cell Nucleus Cell Proliferation Consensus Sequence HeLa Cells Humans I-kappa B Kinase/genetics,metabolism Models, Biological Molecular Sequence Data NF-kappa B/metabolism Neoplasms/etiology Phosphorylation Protein Binding RNA, Small Interfering Serine/metabolism Signal Transduction Transcription, Genetic Transfection Tumor Suppressor Protein p53/metabolism
Chemicals
NF-kappa B RNA, Small Interfering Tumor Suppressor Protein p53 Serine CREB-Binding Protein I-kappa B Kinase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Huang Wei-Chien
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 10018, Taiwan; Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Ju Tsai-Kai
Hung Mien-Chie
Chen Ching-Chow
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/j.molcel.2007.02.019
Published
2007-04-13
Pages
75-87
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2312502
Subset
IM
Grants
NCI NIH HHS · R01 CA109311 · United States
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · CA16672 · United States
NCI NIH HHS · CA099031 · United States
NCI NIH HHS · R01 CA109311-03 · United States
NCI NIH HHS · CA109311 · United States
NCI NIH HHS · P01 CA099031 · United States
NCI NIH HHS · P01 CA099031-04 · United States
Corrections
CommentIn
PMID: 17466617
External Links
PubMed source DOI: 10.1016/j.molcel.2007.02.019 PMC Full Text View journal details
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