Differential recruitment of the mammalian mediator subunit TRAP220 by estrogen receptors ER alpha and ER beta

Citation
A. Warnmark et al., Differential recruitment of the mammalian mediator subunit TRAP220 by estrogen receptors ER alpha and ER beta, J BIOL CHEM, 276(26), 2001, pp. 23397-23404
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
26
Year of publication
2001
Pages
23397 - 23404
Database
ISI
SICI code
0021-9258(20010629)276:26<23397:DROTMM>2.0.ZU;2-E
Abstract
Estrogen receptors (ERs) associate with distinct transcriptional coactivato rs to mediate activation of target genes in response to estrogens. Previous work has provided multiple evidence for a critical role of p160 coactivato rs and associated histone acetyltransferases in estrogen signaling. In cont rast, the involvement of the mammalian mediator complex remains to be estab lished. Further, although the two subtypes ER alpha and ER beta appear to b e similar in regard to principles of LXXLL-mediated coactivator binding to the AF-2 activation domain, there are indications that the context-dependen t transcriptional activation profiles of the two ERs can be quite distinct. Potentially, this could be attributed to differences with regard to coregu lator recruitment. We have here studied the interactions of the nuclear rec eptor-binding subunit of the mammalian mediator complex, referred to as TRA P220, with ER alpha and ER beta. In comparison to the p160 coactivator TIF2 , we find that TRAP220 displays ERP preference. Here, we show that this is a feature of the binding specificity of the TRAP220 LXXLL motifs and demons trate that the ER subtype-specific F-domain influences TRAP220 interaction. Such differences with regard to coactivator recruitment indicate that the relative importance of individual coregulators in estrogen signaling could depend on the dominant ER subtype.