TRANSCRIPTIONAL REGULATION OF HUMAN TRANSGLUTAMINASE1 GENE BY SIGNALING SYSTEMS OF PROTEIN-KINASE-C, RAR RXR AND JUN/FOS IN KERATINOCYTES/

Transglutaminase1 (TGasel) gene is expressed at the late stage of term inal differentiation of epidermal keratinocytes. 12-O-tetradecanoylpho rbol-13-acetate (TPA) markedly induced the luciferase activity in cult ured rat keratinocytes, FRSK cells, transfected with a luciferase repo rter plasmid containing the 0.82-kb 5'-flanking region of the human TG asel gene, but hardly in nonkeratinocytic cells. The TPA-induced lucif erase activity was suppressed by retinoic acid, 9-cis retinoic acid, a nd 1-(5-isoquinolinylsulfonyl)-2-methyylpiperazine (H-7). Co-transfect ion with expression plasmids for c-jun and/or c-fos showed that Jun it self induced the luciferase activity, whereas Fos inhibited both the b asal and TPA-induced luciferase activity. These results suggested that the signaling systems including protein kinase C, retinoic acid/retin oid-X receptors, and Jun/Fos regulate the transcription of the TGase1 gene.