[Regulatory mechanism of steroid hormone receptor functions].
The steroid hormone receptor has been defined as an intracellular protein which associates with the corresponding ligand in a stereospecific manner. Its binding ability and affinity have been reported to be affected by many factors such as protein kinase, SH reducing agent and molybdate. Through ligand binding, hormone-receptor complexes undergo activation process resulting in its acquisition of high affinity toward DNA. Although the detailed biochemical mechanism of receptor activation remains to be elucidated, the reduction of their molecular size has been proposed to be an obligatory step for receptor activation. Recently, heat shock protein 90 K, has become known to bind with the oncogene product (pp 60 v-src). Furthermore, it has been demonstrated to be a common component of both nonactivated, and not activated steroid receptor. The recombinant gene technology has successfully determined the amino acid sequence of GR, ER and PgR. All steroid receptors consist of three domains, namely the immunogenic, DNA-binding and steroid-binding domains. Experiments using deletion mutant receptors revealed that the DNA binding domain has both abilities of DNA binding and transactivation, and that the steroid binding domain negatively regulates DNA binding activity. The purified GR has been found to bind with the specific region (GRE) of glucocorticoid-dependent genes. The consensus sequence of GRE has been observed to be TG-TTCT. Two other proteins which can be associated with some regions near GRE have been proposed to activate cooperatively the glucocorticoid responsive genes with GR. Therefore, the steroid hormone receptor systems are suitable for clarifying the molecular mechanism of gene activation.
Kouhara
H
H
3rd Dept. of Internal Medicine, Osaka University Hospital, Japan.
Sato
B
B
D000818:Animals; D002147:Calmodulin / Q000502:physiology; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology; D015533:Transcriptional Activation
D002147:Calmodulin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D004247:DNA