The phosphorylation site located in the A region of retinoic X receptor alpha is required for the antiproliferative effect of retinoic acid (RA) and the activation of RA target genes in F9 cells

Julie Bastien (1) , Sylvie Adam-Stitah (1) , Jean-Luc Plassat (2) , Pierre Chambon (2) , Cecile Rochette-Egly (2)

1 M.E.N.E.S.R. - Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche
2 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

Mouse F9 embryocarcinoma cells constitute a well established cell autonomous model system for investigating retinoic acid (RA) signaling in vitro. RA induces the differentiation of F9 cells grown as monolayers into endodermal-like cells and decreases their rate of proliferation. Knock-out of the retinoic X receptor alpha (RXRalpha) gene abolishes endodermal differentiation and the induction of several endogenous RA-responsive genes. RXRalpha null cells are also drastically impaired in their antiproliferative response to RA. The role of the RXRalpha phosphorylation site located in the N-terminal A region (Ser(22)) has been investigated here by establishing cell lines re-expressing RXRalpha either wild type or mutated at the phosphorylation site (RXRalphaS22A) in a RXRalpha-null background. We show that Ser(22) is dispensable for RA-induced endodermal differentiation but is crucial for the expression of several RA-responsive genes. Ser(22) is also indispensable for the antiproliferative effect of RA and necessary for the RA-induced down-regulation of p21(CIP) and p27(KIP) CKIs proteins that are known to be involved in the control of cell cycle progression.

Domaines: Biochimie, Biologie Moléculaire

Julie Bastien, Sylvie Adam-Stitah, Jean-Luc Plassat, Pierre Chambon, Cecile Rochette-Egly. The phosphorylation site located in the A region of retinoic X receptor alpha is required for the antiproliferative effect of retinoic acid (RA) and the activation of RA target genes in F9 cells. Journal of Biological Chemistry, 2002, 277 (32), pp.28683-28689. ⟨10.1074/jbc.M203623200⟩. ⟨hal-04131715⟩