Transcriptional activation by oestrogen receptors.
The oestrogen receptor belongs to a superfamily of nuclear receptors that function as hormone-dependent transcription factors. Transcriptional activation is mediated by two activation regions: AF-1 in the N-terminal domain and AF-2 in the ligand binding domain. AF-1, whose activity is also regulated by epidermal growth factor and insulin-like growth factor-I, varies considerably between receptors, whereas AF-2 seems to be conserved in nuclear receptors. From recent structural analysis of the ligand binding domains of two retinoid receptors and the thyroid hormone receptor, it appears that this domain contains a common fold that generates a conserved ligand binding pocket. As a consequence of ligand binding, a C-terminal helix is realigned over the ligand binding pocket to form a novel interacting surface to which co-activators are likely to bind. Several candidate proteins have been identified, including receptor-interacting protein (RIP)-140, RIP-160, transcription intermediary factor (TIF)-1, suppressor of gal4D lesions (SUG)-1 and steroid receptor co-activator (SRC)-1. These proteins interact with receptors only in the presence of their respective hormonal ligands; moreover, their interaction with a series of mutant receptors correlates with their transcriptional activity, suggesting that they may play a role in transcriptional activation. However, only SRC-1 stimulates the transcriptional activity of receptors in transfected mammalian cells, implying that the proteins have different functions. The properties of RIP-140 and SRC-1 will be described and their potential role and mechanism of action discussed.
Parker
M G
MG
Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London, U.K.
D000818:Animals; D001665:Binding Sites; D005786:Gene Expression Regulation; D006801:Humans; D011960:Receptors, Estrogen / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic
D011960:Receptors, Estrogen