CONSTITUTIVELY ACTIVE RETINOID RECEPTORS EXHIBIT INTERFAMILY AND INTRAFAMILY PROMOTER SPECIFICITY

Citation
Tm. Underhill et al., CONSTITUTIVELY ACTIVE RETINOID RECEPTORS EXHIBIT INTERFAMILY AND INTRAFAMILY PROMOTER SPECIFICITY, Molecular endocrinology, 8(3), 1994, pp. 274-285
Citations number
93
Categorie Soggetti
Endocrynology & Metabolism
Journal title
ISSN journal
08888809
Volume
8
Issue
3
Year of publication
1994
Pages
274 - 285
Database
ISI
SICI code
0888-8809(1994)8:3<274:CARREI>2.0.ZU;2-2
Abstract
Retinoid receptors are ligand activated transcription factors that reg ulate gene transcription through a complex network of interactions wit h members of the nuclear hormone receptor superfamily. Although ligand is required for trans-activation, addition of ligand to mammalian cel ls in vitro complicates the study of individual activated retinoid rec eptors. In order to circumvent this problem we have constructed a seri es of retinoid receptors which do not require ligand for trans-activat ion. This was accomplished by fusing the acidic activation domain of t he herpes simplex viral protein VP16 to the carboxyl terminus of indiv idual retinoid receptors. All of the chimeric receptors were found to exhibit constitutive trans-activation activity in CV-1 and P19 cells w hen cotransfected with a reporter that contained a trimerized retinoic acid receptor-beta 2 (RAR beta 2) retinoic acid response element. Fur ther analysis conducted on reporters containing either the RAR beta 2 promoter or the rat cellular retinol binding protein II (rCRBPII) prom oter showed that promoter specificity was well conserved between the c himeric receptors in the absence of exogenous retinoid and their ligan d-induced native counterparts. Moreover, on the RAR beta 2 promoter re porter construct, the chimeric retinoid receptors displayed both cell type and inter- and intrafamily differences in trans-activation, where as, trans-activation of the rCRBPII in the absence of exogenous ligand in CV-1 and P19 cells was found to be stimulated only by chimeric ret inoid X receptor-alpha (RXR alpha). In P19 cells trans-activation of t he rCRBPII promoter by RXR alpha v in the absence of exogenous ligand was inhibited by RAR alpha and the constitutive forms of RAR alpha, RA R beta, RAR gamma, RXR beta, and to a lesser extent RXR gamma.