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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR.

The tumor necrosis factor (TNF) and TNF receptor ( TNFR) gene superfamilies regulate diverse biological functions, including cell proliferation, differentiation, and survival [1] [2] [3]. We have identified a new TNF-related ligand, designated human GITR ligand (hGITRL), and its human receptor (hGITR), an ortholog of the recently discovered murine glucocorticoid-induced TNFR-related (mGITR) protein [4]. The hGITRL gene mapped to chromosome 1q23, near the gene for the TNF homolog Fas/ CD95 ligand [5]. The hGITR gene mapped to chromosome 1p36, near a cluster of five genes encoding TNFR homologs [1] [6]. We found hGITRL mRNA in several peripheral tissues, and detected hGITRL protein on cultured vascular endothelial cells. The levels of hGITR mRNA in tissues were generally low; in peripheral blood T cells, however, antigen-receptor stimulation led to a substantial induction of hGITR transcripts. Cotransfection of hGITRL and hGITR in embryonic kidney 293 cells activated the anti-apoptotic transcription factor NF-kappaB, via a pathway that appeared to involve TNFR-associated factor 2 ( TRAF2) [7] and NF-kappaB-inducing kinase (NIK) [8]. Cotransfection of hGITRL and hGITR in Jurkat T leukemia cells inhibited antigen-receptor-induced cell death. Thus, hGITRL and hGITR may modulate T lymphocyte survival in peripheral tissues.[1]


  1. Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR. Gurney, A.L., Marsters, S.A., Huang, R.M., Pitti, R.M., Mark, D.T., Baldwin, D.T., Gray, A.M., Dowd, A.D., Brush, A.D., Heldens, A.D., Schow, A.D., Goddard, A.D., Wood, W.I., Baker, K.P., Godowski, P.J., Ashkenazi, A. Curr. Biol. (1999) [Pubmed]
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