Multiple mechanisms of growth hormone-regulated gene transcription

• Autores: Ceseña, Teresa I.; Cui, Tracy Xiao; Piwien Pilipuk, Graciela; Kaplani, Julianne; Calinescu, Anda Alexandra; Huo, Jeffrey S.; Iñiguez Lluhí, Jorge A.; Kwok, Roland; Schwartz, Jessica
• Año de publicación: 2007
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: GH; C/EBPbeta; GENE EXPRESSION; NUCLEOPROTEINS; TRANSCRIPTION FACTORS
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Diverse 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.
Fil: Ceseña, Teresa I.. University of Michigan; Estados Unidos
Fil: Cui, Tracy Xiao. University of Michigan; Estados Unidos
Fil: Piwien Pilipuk, Graciela. Fundación Instituto Leloir; Argentina
Fil: Kaplani, Julianne. University of Michigan; Estados Unidos
Fil: Calinescu, Anda Alexandra. Michigan State University; Estados Unidos
Fil: Huo, Jeffrey S.. University of Michigan; Estados Unidos
Fil: Iñiguez Lluhí, Jorge A.. University of Michigan; Estados Unidos
Fil: Kwok, Roland. University of Michigan; Estados Unidos
Fil: Schwartz, Jessica. University of Michigan; Estados Unidos