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Multiple mechanisms of growth hormone-regulated gene transcription Cesena TI; Cui TX; Piwien-Pilipuk G; Kaplani J; Calinescu AA; Huo JS; Iniguez-Lluhi JA; Kwok R; Schwartz JMol Genet Metab 2007[Feb]; 90 (2): 126-33Diverse physiological actions of growth hormone (GH) are mediated by changes in gene transcription. Transcription can be regulated at several levels, including post-translational modification of transcription factors, and formation of multiprotein complexes involving transcription factors, co-regulators and additional nuclear proteins; these serve as targets for regulation by hormones and signaling pathways. Evidence that GH regulates transcription at multiple levels is exemplified by analysis of the proto-oncogene c-fos. Among the GH-regulated transcription factors on c-fos, C/EBPbeta appears to be key, since depletion of C/EBPbeta by RNA interference blocks the stimulation of c-fos by GH. The phosphorylation state of C/EBPbeta and its ability to activate transcription are regulated by GH through MAPK and PI3K/Akt-mediated signaling cascades. The acetylation of C/EBPbeta also contributes to its ability to activate c-fos transcription. These and other post-translational modifications of C/EBPbeta appear to be integrated for regulation of transcription by GH. The formation of nuclear proteins into complexes associated with DNA-bound transcription factors is also regulated by GH. Both C/EBPbeta and the co-activator p300 are recruited to c-fos in response to GH, altering c-fos promoter activation. In addition, GH rapidly induces spatio-temporal re-localization of C/EBPbeta within the nucleus. Thus, GH-regulated gene transcription mediated by C/EBPbeta reflects the integration of diverse mechanisms including post-translational modifications, modulation of protein complexes associated with DNA and re-localization of gene regulatory proteins. Similar integration involving other transcription factors, including Stats, appears to be a feature of regulation by GH of other gene targets.|*Gene Expression Regulation[MESH]|*Transcription, Genetic[MESH]|Animals[MESH]|CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism[MESH]|Genes, fos[MESH]|Growth Hormone/*metabolism[MESH]|Humans[MESH]|Nucleoproteins/chemistry/metabolism[MESH]|Protein Processing, Post-Translational[MESH]|Proto-Oncogene Mas[MESH]|Transcription Factors/genetics/metabolism[MESH] |
