Stat3 Activation of NF-κB p100 Processing Involves CBP/p300-Mediated Acetylation

Activation of the noncanonical NF-κB signaling pathway involved in the proteolytic processing of NF-κB p100 to p52 is tightly regulated, and overproduction of p52 leads to lymphocyte hyperplasia and transformation. We have demonstrated that active but not latent Stat3, expressed in many types of hum...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-05, Vol.103 (19), p.7264-7269
Main Authors: Nadiminty, Nagalakshmi, Lou, Wei, Lee, Soo Ok, Lin, Xin, Trump, Donald L., Gao, Allen C.
Format: Article
Language:English
Subjects:
Acetylation
Antibodies
Apoptosis
Biological Sciences
Cell death
DNA
HEK293 cells
Phosphorylation
Plasmids
Proteins
Small interfering RNA
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Summary:Activation of the noncanonical NF-κB signaling pathway involved in the proteolytic processing of NF-κB p100 to p52 is tightly regulated, and overproduction of p52 leads to lymphocyte hyperplasia and transformation. We have demonstrated that active but not latent Stat3, expressed in many types of human cancers involved in cell proliferation and survival, induces p100 processing to p52 by activation of IKKα and subsequent phosphorylation of p100. The Stat3-mediated p100 processing to p52 requires activation of Stat3 by the acetyltransferase activity of cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300. A mutant of Stat3 defective in acetylation blocked Stat3-mediated p100 processing to p52 and acted as a dominant negative in blocking the production of p52. Furthermore, overexpression of p52 protected cells from apoptotic cell death. Thus, activation of the processing of p100 to p52 by Stat3 may represent one of the common pathways used by cancer cells to survive and escape therapy.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0509808103