Article: article from journal or magazin.
Glucocorticoid-induced tumor necrosis factor receptor is a p21Cip1/WAF1 transcriptional target conferring resistance of keratinocytes to UV light-induced apoptosis.
Journal of Biological Chemistry
Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a member of the tumor necrosis factor receptor superfamily, is expressed in T lymphocytes, and exerts an anti-apoptotic function in these cells. We reported that GITR is also highly expressed in the skin, specifically in keratinocytes, and that it is under negative transcriptional control of p21(Cip1/WAF1), independently from the cell cycle. Although GITR expression is higher in p21-deficient keratinocytes and skin, it is down-modulated with differentiation and in response to UVB. The combined analysis of keratinocytes with increased GITR expression versus normal keratinocytes and skin of mice with a disruption of the GITR gene indicates that this protein protects keratinocytes from UVB-induced apoptosis both in vitro and in vivo.
Animals, Apoptosis/radiation effects, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p21/genetics, Cyclin-Dependent Kinase Inhibitor p21/metabolism, Epidermis/cytology, Epidermis/metabolism, Female, Gene Deletion, Glucocorticoids/pharmacology, Keratinocytes/cytology, Keratinocytes/radiation effects, Mice, Receptors, Nerve Growth Factor/metabolism, Receptors, Tumor Necrosis Factor/metabolism, Transcription, Genetic, Ultraviolet Rays
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