Glucocorticoid-induced tumor necrosis factor receptor is a p21Cip1/WAF1 transcriptional target conferring resistance of keratinocytes to UV light-induced apoptosis.
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.
Wang
Jian
J
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, 02129, USA.
Devgan
Vikram
V
Corrado
Marcella
M
Prabhu
Nita S
NS
El-Deiry
Wafik S
WS
Riccardi
Carlo
C
Pandolfi
Pier Paolo
PP
Missero
Caterina
C
Dotto
G Paolo
GP
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D017353:Gene Deletion; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000528:radiation effects*; D051379:Mice; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse