Molecular cloning and characterization of two novel human RXR alpha splice variants.
Two novel cDNAs encoding RXR alpha splice variants (RXR alpha 2 and RXR alpha 3) were identified among human full-length cDNA libraries. RXR alpha 2 and RXR alpha 3 cDNAs possess open reading frames, leading to production of proteins lacking the N-terminal 27 and 97 amino acid residues of the RXR alpha 1 product, respectively. RXR alpha 2 and RXR alpha 3 genes have respective 5'-terminal exons. RXR alpha 3 is expressed in brain, spleen and prostate whereas the expression of RXR alpha 2 was below the detectable level. Both RXR alpha 2 and RXR alpha 3 showed a level of transcriptional activity and a dose response curve against the agonist LG100268 similar to RXR alpha 1 in reporter assay for the RXR alpha homodimer or that for the heterodimer with PPAR gamma 2. 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 PGC-1. These results suggest specific physiological roles of two novel human RXR alpha splice variants.
Kojo
Hitoshi
H
Advanced Technology Platform Research Laboratory, Fujisawa Pharmaceutical Co. Ltd., Tsukuba, Ibaraki 300-2698, Japan. kojo@biomarker.co.jp
Tajima
Kaoru
K
Fukagawa
Masao
M
Isogai
Takao
T
Nishimura
Shintaro
S
D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D009539:Nicotinic Acids / Q000494:pharmacology; D009928:Organ Specificity; D047490:Retinoid X Receptor alpha / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D018076:DNA, Complementary; D009539:Nicotinic Acids; D047490:Retinoid X Receptor alpha; D013764:Tetrahydronaphthalenes; C095104:LG 100268