06(9.432)stat3激活的NF-KBp100加工参与到了CBPp300调节的乙酰化作用中.pdf

Stat3 activation of NF-B p100 processing involves CBPp300-mediated acetylation † ‡ Nagalakshmi Nadiminty*, Wei Lou*, Soo Ok Lee*, Xin Lin , Donald L. Trump*, and Allen C. Gao* *Departments of Medicine, Pharmacology, and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263; and †Department of Molecular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 Edited by Victoria M. Richon, Merck Co., Boston, MA, and accepted by the Editorial Board April 1, 2006 (received for review November 11, 2005) Activation of the noncanonical NF-B signaling pathway involved processing of p105 to p50 is constitutive, the processing of p100 in the proteolytic processing of NF-B p100 to p52 is tightly to p52 is a tightly controlled event in many cells and tissues regulated, and overproduction of p52 leads to lymphocyte hyper- (14–17). plasia and transformation. We have demonstrated that active but Although processing of p100 to p52 is usually tightly regulated, not latent Stat3, expressed in many types of human cancers this proteolytic processing can be activated by lymphotoxin (18, involved in cell proliferation and survival, induces p100 processing 19), B cell-activating factor (20, 21), CD40 ligand (19, 22), and to p52 by activation of IKK and subsequent phosphorylation of its cis-acting domain (17). Constitutive processing of p100 pro- p100. The Stat3-mediated p100 processing to p52 requires activa- tein resulting in overexpression of p52 leads to lymphocyte tion of Stat3 by the acetyltransferase activity of cAMP-response hyperplasia and transformation (9, 22, 23). Here we show that element-binding protein (C