Molecular Endocrinology, Vol 7, 387-398, Copyright © 1993 by Endocrine Society

ARTICLES

Regulation of transglutaminase type I expression in squamous differentiating rabbit tracheal epithelial cells and human epidermal keratinocytes: effects of retinoic acid and phorbol esters

NA Saunders, SH Bernacki, TM Vollberg and AM Jetten
Cell Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park, North Carolina 27709.

In the present study we describe the full length cDNA sequence for rabbit transglutaminase type I as well as the sequence for a 2.9- kilobase (kb) promoter fragment of the gene. Transglutaminase type I mRNA expression was inhibited in squamous differentiating epithelia by retinoic acid (RA) in a dose-dependent (EC50 = 1-2 nM) and transcriptional manner. In human epidermal keratinocytes transglutaminase type I mRNA was induced by 12-O-tetradecanoylphorbol- 13-acetate (TPA) treatment, and this induction could be inhibited by bryostatin 1. In contrast, TPA treatment inhibited the expression of c- myc mRNA. Bryostatin 1 but not RA could prevent this decrease in c-myc mRNA expression, indicating that transglutaminase type I mRNA expression was associated with differentiation and not growth arrest. An SP1 element was found within 50 base pairs 5' of the transcription initiation site. A TATA-like element (CATAAAC) was found but was not capable of activating transcription. In addition, putative response elements for C-MYC, Ker1/AP2, 2 AP1 sites, a CK-8-mer, and an AP2 site were present in the 2.9-kb fragment. Transfection of RbTE cells with the 2.9-kb fragment ligated to a promoterless luciferase vector resulted in 2.2-fold more luciferase expression in differentiated vs. undifferentiated cells. Furthermore, luciferase activity was induced 7.4-fold in human epidermal keratinocytes induced to differentiate with TPA. TPA-induced luciferase activity was inhibited by both bryostatin 1 and RA. No known RA response elements were identified in the promoter.(ABSTRACT TRUNCATED AT 250 WORDS)

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