Transcriptional regulation by steroid receptor coactivator phosphorylation.
The basic mechanisms underlying ligand-dependent transcriptional activation by nuclear receptors (NRs) require the sequential recruitment of various coactivators. Increasing numbers of coactivators have been identified in recent years, and both biochemical and genetic studies demonstrate that these coactivators are differentially used by transcription factors, including NRs, in a cell/tissue type- and promoter-specific manner. However, the molecular basis underlying this specificity remains largely unknown. Recently, NRs and coregulators were shown to be targets of posttranslational modifications activated by diverse cellular signaling pathways. It is argued that posttranslational modifications of these proteins provide the basis for a combinatorial code required for specific gene activation by NRs and coactivators, and that this code also enables coactivators to efficiently stimulate the activity of other classes of transcription factors. In this review, we will focus on coactivators and discuss the recent progress in understanding the role of phosphorylation of the steroid receptor coactivator family and the potential ramifications of this posttranslational modification for regulation of gene expression.
Wu
Ray-Chang
RC
Molecular and Cellular Biology, One Baylor Plaza, Houston, Texas 77030, USA. carolyns@bcm.tmc.edu
Smith
Carolyn L
CL
O'Malley
Bert W
BW
D000123:Acetyltransferases; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D051548:Histone Acetyltransferases; D006801:Humans; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins; D010766:Phosphorylation; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation
D051958:Nuclear Receptor Coactivator 2; D015513:Oncogene Proteins; D011987:Receptors, Steroid; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538866:NCOA3 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3