- Transglutaminase 1 (TGase 1) is expressed during the terminal differentiation of keratinized squamous epithelium to form cornified cell envelope in differentiated keratinocytes by the -(-glutamyl) cross-linking reaction. The gene for human TGase 1 is responsible for autosomal recessive lamellar ichthyosis, a severe hereditary keratinizing disorder of the skin. We examined the transcriptional activity of the gene in FRSK, rat keratinocytic cells, transfected with the luciferase reporter gene under control of the 5′ upstream region of human TGase 1 gene. Transfection of the reporter gene with an expression vector for the isoform of novel protein kinase C (nPKC), as well as exposure to 12-O-tetradecanoylphorbol-13-acetate, markedly increased the luciferase activity in FRSK, but not in HT-1080 fibrosarcoma cells, although exogenous nPKC was expressed in both. The induction was suppressed by deleting the TGase 1 upstream sequence from −95 to −67 and by deleting the kinase domain from exogenous nPKC. In comparison with other PKC isoforms, nPKC most effectively induced the luciferase activity. We suggest that nPKC, an epithelium-specific isoform of PKC, mediates the activation of the TGase 1 transcription.