Molecular cloning and characterization of two novel human RXRα splice variants

Two novel cDNAs encoding RXRalpha splice variants (RXRalpha2 and RXRalpha3) were identified among human full-length cDNA libraries. RXRalpha2 and RXRalpha3 cDNAs possess open reading frames, leading to production of proteins lacking the N-terminal 27 and 97 amino acid residues of the RXRalpha1 product, respectively. RXRalpha2 and RXRalpha3 genes have respective 5-terminal exons. RXRalpha3 is expressed in brain, spleen and prostate whereas the expression of RXRalpha2 was below the detectable level. Both RXRalpha2 and RXRalpha3 showed a level of transcriptional activity and a dose response curve against the agonist LG100268 similar to RXRalpha1 in reporter assay for the RXRalpha homodimer or that for the heterodimer with PPARgamma2. However, clear differences were observed among the splice variants when dose response curves were compared by the assay in the presence of coactivators such as SRC-1 and PGG-1. These results suggest specific physiological roles of two novel human RXRalpha splice variants. (C) 2004 Elsevier Ltd. All rights reserved.