Molecular Endocrinology, Vol 8, 274-285, Copyright © 1994 by Endocrine Society

ARTICLES

Constitutively active retinoid receptors exhibit interfamily and intrafamily promoter specificity

TM Underhill, DE Cash and E Linney
Department of Microbiology, Duke University, Durham, North Carolina 27710.

Retinoid receptors are ligand activated transcription factors that regulate gene transcription through a complex network of interactions with members of the nuclear hormone receptor superfamily. Although ligand is required for trans-activation, addition of ligand to mammalian cells in vitro complicates the study of individual activated retinoid receptors. In order to circumvent this problem we have constructed a series of retinoid receptors which do not require ligand for trans-activation. This was accomplished by fusing the acidic activation domain of the herpes simplex viral protein VP16 to the carboxyl terminus of individual retinoid receptors. All of the chimeric receptors were found to exhibit constitutive trans-activation activity in CV-1 and P19 cells when cotransfected with a reporter that contained a trimerized retinoic acid receptor-beta 2 (RAR beta 2) retinoic acid response element. Further analysis conducted on reporters containing either the RAR beta 2 promoter or the rat cellular retinol binding protein II (rCRBPII) promoter showed that promoter specificity was well conserved between the chimeric receptors in the absence of exogenous retinoid and their ligand-induced native counterparts. Moreover, on the RAR beta 2 promoter reporter construct, the chimeric retinoid receptors displayed both cell type and inter- and intrafamily differences in trans-activation, whereas, 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 retinoid X receptor-alpha (RXR alpha). In P19 cells trans-activation of the rCRBPII promoter by RXR alpha v in the absence of exogenous ligand was inhibited by RAR alpha and the constitutive forms of RAR alpha, RAR beta, RAR gamma, RXR beta, and to a lesser extent RXR gamma.

This article has been cited by other articles:

				C. Wongtrakool, S. Malpel, J. Gorenstein, J. Sedita, M. I. Ramirez, T. M. Underhill, and W. V. Cardoso Down-regulation of Retinoic Acid Receptor {alpha} Signaling Is Required for Sacculation and Type I Cell Formation in the Developing Lung J. Biol. Chem., November 21, 2003; 278(47): 46911 - 46918. [Abstract] [Full Text] [PDF]

				N. B. McDermott, D. F. Gordon, C. A. Kramer, Q. Liu, E. Linney, W. M. Wood, and B. R. Haugen Isolation and Functional Analysis of the Mouse RXRgamma 1 Gene Promoter in Anterior Pituitary Cells J. Biol. Chem., September 20, 2002; 277(39): 36839 - 36844. [Abstract] [Full Text] [PDF]

				A. D. Weston, R. A.S. Chandraratna, J. Torchia, and T. M. Underhill Requirement for RAR-mediated gene repression in skeletal progenitor differentiation J. Cell Biol., July 8, 2002; 158(1): 39 - 51. [Abstract] [Full Text] [PDF]

				A. D. Weston, V. Rosen, R. A.S. Chandraratna, and T. M. Underhill Regulation of Skeletal Progenitor Differentiation by the Bmp and Retinoid Signaling Pathways J. Cell Biol., February 21, 2000; 148(4): 679 - 690. [Abstract] [Full Text] [PDF]

				H. Wan, N. Oridate, D. Lotan, W. K. Hong, and R. Lotan Overexpression of Retinoic Acid Receptor {beta} in Head and Neck Squamous Cell Carcinoma Cells Increases Their Sensitivity to Retinoid-induced Suppression of Squamous Differentiation by Retinoids Cancer Res., July 1, 1999; 59(14): 3518 - 3526. [Abstract] [Full Text] [PDF]

				H. Wan, M. I. Dawson, W. K. Hong, and R. Lotan Overexpressed Activated Retinoid X Receptors Can Mediate Growth Inhibitory Effects of Retinoids in Human Carcinoma Cells J. Biol. Chem., October 9, 1998; 273(41): 26915 - 26922. [Abstract] [Full Text] [PDF]

				R. A. Spanjaard, M. Ikeda, P. J. Lee, B. Charpentier, W. W. Chin, and T. J. Eberlein Specific Activation of Retinoic Acid Receptors (RARs) and Retinoid X Receptors Reveals a Unique Role for RARgamma in Induction of Differentiation and Apoptosis of S91 Melanoma Cells J. Biol. Chem., July 25, 1997; 272(30): 18990 - 18999. [Abstract] [Full Text] [PDF]

				J.-H. Xiao, Béa. Durand, P. Chambon, and J. J. Voorhees Endogenous Retinoic Acid Receptor (RAR)-Retinoid X Receptor (RXR) Heterodimers Are the Major Functional Forms Regulating Retinoid-responsive Elements in Adult Human Keratinocytes J. Biol. Chem., February 17, 1995; 270(7): 3001 - 3011. [Abstract] [Full Text] [PDF]