Details

Autor(en) / Beteiligte

• AOUDJIT, F
• BROCHU, N
• MORIN, N
• POULIN, G
• STRATOWA, C
• AUDETTE, M

Titel

Heterodimeric retinoic acid receptor-β and retinoid X receptor-α complexes stimulate expression of the intercellular adhesion molecule-1 gene

Ist Teil von

• Cell growth & differentiation, 1995-05, Vol.6 (5), p.515-521

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

1995

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.