[ XXXX : mechanisms of action].

@entity14028 @entity4878 @entity13351 @entity35406 @entity554 @entity904 @entity10211 @entity555 @entity15464 @entity5995 @entity1968 @entity8620
@entity4878 , @entity904 derivatives, are natural or synthetic molecules with pleiotropic effects, which regulate cell differentiation, proliferation and apoptosis. In target cell, the active natural metabolites @entity1968 (RA) and @entity8620 are synthetized from @entity904 by a two-step process with intermediate metabolite @entity5995 . In 1987, the identification of the nuclear @entity1968 receptors that belong to the superfamily of nuclear receptors led to a significant progress in the comprehension of the mechanism of action of @entity4878 . There are two families of @entity554 Nuclear Receptors (RNR), the RA receptors (RAR), which natural ligand is RA, and the @entity13351 ( @entity13351 ), which natural ligand is @entity8620 . Among synthetic @entity4878 , @entity10211 , @entity14028 , @entity555 and @entity15464 are ligands of the RAR, @entity35406 is the first rexinoid (ligand of the @entity13351 ), alitretinoin the first panagonist (RAR+ @entity13351 ). For each family, there are 3 isotypes (a, b, y), and for each isotype several isoforms. Each NRR is composed of 6 regions (A-F). 3 regions are of importance: the A/B region has a ligand-independent transcriptional activation function, the C region harbors the DNA binding domain, the E region harbors the ligand binding domain. To regulate the expression of target genes, NRR have to dimerize. @entity13351 are obligatory in dimers (heterodimers RAR- @entity13351 , homodimers @entity13351 - @entity13351 ). Dimers binds specific sequences of DNA, present in the promoters of target genes. When the ligand, natural or synthetic, bind to RNR, coactivators are recruited and transcription factors are activated. In target cell, @entity4878 not utilized are degradated in polar metabolites by enzymes of cytochrome P450.
