[Hormonal regulation of gene transcription--specificity and regulation of the hormonal response and results of its dysfunction].
Nuclear hormone receptors act as ligand activated transcription factors. Hormonal response in vivo is, however, modulated at various levels beyond the mere activation of hormone receptors by their respective ligands. There is a great variability of particular arrangements of HRE and receptors of the TR/RAR subfamily use extensive dimerization to produce a particular dimer with optimal affinity for HRE in question. Hormonal response is mediated by complex hormone responsive units (HRU), which integrate HRE together with other regulatory sequences. Some hormone responsive genes may themselves code transcription factors or other regulatory proteins, underlying delayed primary and secondary responses. In addition to transcription activation, nuclear receptors enter repressive interactions with unrelated transcription factors like AP-1 or NF-kappa B. Genes for coding nuclear receptors are subjected to homologous downregulation. Functioning of nuclear receptors might be modulated by phosphorylation, which can underly ligand-independent activation. Nuclear receptors are mutated and/or disregulated in various pathologies, like hormone resistance syndromes of cancer.
Hatina
J
J
Ustav biologie LF UK, Plzen.
Reischig
J
J
D000818:Animals; D006728:Hormones / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D010766:Phosphorylation; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation
D006728:Hormones; D011987:Receptors, Steroid