Abstract
Tissue transglutaminase (transglutaminase type II) is an intracellular protein cross-linking enzyme that accumulates in connective tissue and in cells undergoing apoptosis. Retinoids regulate the transcription of the mouse tissue transglutaminase gene via activation of regulatory elements contained within 4 kilobases of the 5'-end of the gene. Co-transfection studies with retinoid receptor expression vectors in CV-1 cells demonstrated that the mouse tissue transglutaminase promoter is activated by ligand activation of either retinoic acid receptor-retinoid X receptor (RAR.RXR) heterodimers or RXR homodimers. Optimal induction is achieved with retinoid receptor panagonists; partial activation can also be achieved with either RAR-specific or RXR-specific retinoids. Retinoid-dependent activation of the tissue transglutaminase promoter depends on both a proximal regulatory region containing sequences highly conserved between the human and the mouse tissue transglutaminase promoters and a distal region that includes a 30-base pair retinoid response element (mTGRRE1). mTGRRE1 contains three hexanucleotide half-sites (two canonical and one non-canonical) in a DR7/DR5 motif that bind both RAR*RXR heterodimers and RXR homodimers. These studies suggest that retinoid-dependent expression of the mouse tissue transglutaminase gene is mediated by a versatile tripartite retinoid response element located 1.7 kilobases upstream of the transcription start site.
Highlights
Tissue transglutaminase is an intracellular protein cross-linking enzyme that accumulates in connective tissue and in cells undergoing apoptosis
We have found that this retinoid response element is versatile, capable of binding to and being activated by both RAR1⁄7RXR heterodimer and retinoid X receptors (RXRs) homodimer receptor complexes
all-trans retinoic acid (ATRA) induced a 10-fold increase in -galactosidase activity in cells transfected with pmTG3.8-LacF, whereas it had no effect on the activity of cells transfected with the control vector, pBasic-LacF
Summary
Tissue transglutaminase (transglutaminase type II) is an intracellular protein cross-linking enzyme that accumulates in connective tissue and in cells undergoing apoptosis. Retinoids regulate the transcription of the mouse tissue transglutaminase gene via activation of regulatory elements contained within 4 kilobases of the 5-end of the gene. Co-transfection studies with retinoid receptor expression vectors in CV-1 cells demonstrated that the mouse tissue transglutaminase promoter is activated by ligand activation of either retinoic acid receptor-retinoid X receptor (RAR1⁄7RXR) heterodimers or RXR homodimers. MTGRRE1 contains three hexanucleotide half-sites (two canonical and one non-canonical) in a DR7/DR5 motif that bind both RAR1⁄7RXR heterodimers and RXR homodimers These studies suggest that retinoid-dependent expression of the mouse tissue transglutaminase gene is mediated by a versatile tripartite retinoid response element located 1.7 kilobases upstream of the transcription start site. Tissue transglutaminase-mediated cross-linking of intracellular proteins occurs in cells undergoing apoptotic or programmed cell death [7, 8]. TGF- and retinoids induce transglutaminase activity in tracheal epithelial cells [20, 21], and IL-6 induces the enzyme in hepatocytes [22]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have