Heterodimeric retinoic acid receptor-beta and retinoid X receptor-alpha complexes stimulate expression of the intercellular adhesion molecule-1 gene.
Human intercellular adhesion molecule-1 (ICAM-1), a specific ligand for the leukocyte-function associated antigen-1 and for Mac-1, plays an important role in immune responses. ICAM-1 expression is regulated by various proinflammatory cytokines, phorbol myristate acetate, and retinoic acid. In this study, we investigated the mechanisms of transcriptional control involved in the stimulation of ICAM-1 gene expression by retinoic acid in Cos-1 cells. Deletion mutant analysis provided evidence that a region located between -393 and -176 from the translational start site is critical to retinoic acid stimulation of luciferase activity. This region harbors the consensus sequence for a retinoic acid-responsive element (RARE) 5'-GGGTCATCGCCCTGCCA-3'. The Smal(-270)/Smal (-178) fragment containing this element conferred appropriate retinoic acid responsiveness to an enhancerless SV40 promoter. Cotransfection of expression vectors encoding the retinoic acid receptor alpha, beta, or gamma and retinoid X receptor alpha with reporter plasmids harboring the putative RARE demonstrated that the ICAM-1 gene is regulated by retinoic acid in a retinoic acid receptor beta/retinoid X receptor alpha-dependent fashion. Electrophoretic mobility shift assays showed that ICAM-1 and ADH3 RARE, a well-characterized RARE, display the same band shift pattern, bind retinoic acid receptor beta and retinoid X receptor alpha, and are mutually competitive.
Aoudjit
F
F
Department of Biochemistry, Laval University, Quebec, Canada.
Brochu
N
N
Morin
N
N
Poulin
G
G
Stratowa
C
C
Audette
M
M
D001483:Base Sequence; D001667:Binding, Competitive; D002478:Cells, Cultured; D016384:Consensus Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D047488:Retinoid X Receptors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology
D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C082925:retinoic acid receptor beta; D018799:Intercellular Adhesion Molecule-1; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate