F. Aoudjit et al., HETERODIMERIC RETINOIC ACID RECEPTOR-BETA AND RETINOID-X RECEPTOR-ALPHA COMPLEXES STIMULATE EXPRESSION OF THE INTERCELLULAR-ADHESION MOLECULE-1 GENE, Cell growth & differentiation, 6(5), 1995, pp. 515-521
Human intercellular adhesion molecule-1 (ICAM-1), a specific ligand fo
r 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 reti
noic acid. In this study, we investigated the mechanisms of transcript
ional control involved in the stimulation of ICAM-1 gene expression by
retinoic acid in Cos-l cells. Deletion mutant analysis provided evide
nce that a region located between -393 and -176 from the translational
start site is critical to retinoic acid stimulation of luciferase act
ivity. 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 retinoi
c 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 harbor
ing the putative RARE demonstrated that the ICAM-1 gene is regulated b
y retinoic acid in a retinoic acid receptor beta/retinoid X receptor a
lpha-dependent fashion. Electrophoretic mobility shift assays showed t
hat ICAM-1 and ADH3 RARE, a well-characterized RARE, display the same
band shift pattern, bind retinoic acid receptor beta and retinoid X re
ceptor alpha, and are mutually competitive.