Molecular Cell
Volume 26, Issue 1, 13 April 2007, Pages 75-87
Journal home page for Molecular Cell

Article
Phosphorylation of CBP by IKKα Promotes Cell Growth by Switching the Binding Preference of CBP from p53 to NF-κB

https://doi.org/10.1016/j.molcel.2007.02.019Get rights and content
Under an Elsevier user license
open archive

Summary

CBP plays a central role in coordinating and integrating multiple signaling pathways. Competition between NF-κB 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 IKKα phosphorylates CBP at serine 1382 and serine 1386 and consequently increases CBP's HAT and transcriptional activities. Importantly, such phosphorylation enhances NF-κB-mediated gene expression and suppresses p53-mediated gene expression by switching the binding preference of CBP from p53 to NF-κB, thus promoting cell growth. The CBP phosphorylation also correlates with constitutive IKKα activation in human lung tumor tissue compared with matched nontumor lung tissue. Our results suggest that phosphorylation of CBP by IKKα regulates the CBP-mediated crosstalk between NF-κB and p53 and thus may be a critical factor in the promotion of cell proliferation and tumor growth.

DNA
SIGNALING
CELLCYCLE

Cited by (0)