Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / radiation effects*
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
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Epidermal Cells
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Epidermis / metabolism
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Epidermis / radiation effects
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Female
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Gene Deletion
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Glucocorticoid-Induced TNFR-Related Protein
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Glucocorticoids / pharmacology*
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Keratinocytes / cytology
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Keratinocytes / radiation effects*
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Mice
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Receptors, Nerve Growth Factor / metabolism*
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Receptors, Tumor Necrosis Factor / metabolism*
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Transcription, Genetic*
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Ultraviolet Rays*
Substances
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Glucocorticoid-Induced TNFR-Related Protein
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Glucocorticoids
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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Tnfrsf18 protein, mouse