SMRT Derepression by the IκB Kinase α A Prerequisite to NF-κB Transcription and Survival.pdfVIP

Molecular Cell, Vol. 16, 245–255, October 22, 2004, Copyright 2004 by Cell Press SMRT Derepression by the IB Kinase : A Prerequisite to NF-B Transcription and Survival Jamie E. Hoberg,1 1 1, Fan Yeung, and Marty W. Mayo * et al., 2002). Acetylation of the RelA/p65 protein is impor- 1Department of Biochemistry and Molecular Genetics tant for DNA binding and transactivation potential as The University of Virginia well as IB interaction and nuclear export (Chen et al., Charlottesville, Virginia 22908 2002; Kiernan et al., 2003). The transcriptional activity of RelA/p65 is modulated by histone deacetylases (HDACs), including HDAC1, HDAC2, HDAC3, and SIRT1 Summary (Ashburner et al., 2001; Yeung et al., 2004; Chen et al., 2001). Understanding how signaling cascades stimulate chro- Transcriptional repression is regulated by three HDAC matin-remodeling events through derepression is one classes (Gray and Ekstrom, 2001). Class I includes of the foremost questions in the transcription field. HDAC1, HDAC2, HDAC3, and HDAC8; class II includes Here, we demonstrate that NF-B transcription re- HDAC4, HDAC5, HDAC6, HDAC7, and HDAC9; and class quires IKK to phosphorylate SMRT on chromatin, III includes the Hub-2 homologs and Sirtuins, including stimulating the exchange of corepressor for coactiva- SIRT1. The enzymatic activity of class I and II HDACs tor