Transcriptional Regulation by Steroid Receptor Coactivator Phosphorylation
Ray-Chang Wu,
Carolyn L. Smith and
Bert W. O’Malley
Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030
Correspondence: Address all correspondence and requests for reprints to: Carolyn L. Smith, Ph.D., Molecular and Cellular Biology, One Baylor Plaza, Houston, Texas 77030. E-mail: carolyns{at}bcm.tmc.edu
The basic mechanisms underlying ligand-dependent transcriptionalactivation by nuclear receptors (NRs) require the sequentialrecruitment of various coactivators. Increasing numbers of coactivatorshave been identified in recent years, and both biochemical andgenetic studies demonstrate that these coactivators are differentiallyused by transcription factors, including NRs, in a cell/tissuetype- and promoter-specific manner. However, the molecular basisunderlying this specificity remains largely unknown. Recently,NRs and coregulators were shown to be targets of posttranslationalmodifications activated by diverse cellular signaling pathways.It is argued that posttranslational modifications of these proteinsprovide the basis for a combinatorial code required for specificgene activation by NRs and coactivators, and that this codealso enables coactivators to efficiently stimulate the activityof other classes of transcription factors. In this review, wewill focus on coactivators and discuss the recent progress inunderstanding the role of phosphorylation of the steroid receptorcoactivator family and the potential ramifications of this posttranslationalmodification for regulation of gene expression.
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