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| REGULATION OF TRANSGLUTAMINASE TYPE-I EXPRESSION IN SQUAMOUS DIFFERENTIATING RABBIT TRACHEAL EPITHELIAL-CELLS AND HUMAN EPIDERMAL-KERATINOCYTES - EFFECTS OF RETINOIC ACID AND PHORBOL ESTERS |
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| Author(s): SAUNDERS NA, BERNACKI SH, VOLLBERG TM, JETTEN AM |
| Source: MOLECULAR ENDOCRINOLOGY Volume: 7 Issue: 3 Pages: 387-398 Published: MAR 1993 |
| Times Cited: 77 References: 48 |
| Abstract: 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. These data indicate that response elements mediating differentiation-specific expression, retinoid sensitivity, and phorbol ester responsiveness of transglutaminase type I gene expression are contained within the proximal 2.9 kb of the promoter. |
| Document Type: Article |
| Language: English |
Addresses:
1. NIEHS, PULM PATHOBIOL LAB, CELL BIOL SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA |
| Publisher: ENDOCRINE SOC, 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: KU730 |
| ISSN: 0888-8809 |
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