Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 24, pp 3087–3092 | Cite as

TRAF4 functions as an intermediate of GITR-induced NF-κB activation

  • E. M. Esparza
  • R. H. ArchEmail author
Research Article


Members of the tumor necrosis factor receptor (TNFR) family regulate the activation, differentiation, and function of many cell types, including cells of the immune system. TNFR-associated factors (TRAFs) function as adapter molecules controlling signaling pathways triggered by TNFR family members, such as activation of nuclear factor κB (NF-κB). Despite intensive research, the function of TRAF4 in signaling pathways triggered by TNFR-related proteins remains enigmatic. Intriguingly, our functional studies indicated that TRAF4 augments NF-κB activation triggered by glucocorticoid-induced TNFR (GITR), a receptor expressed on T cells, B cells, and macrophages. Further analyses revealed that TRAF4-mediated NF-κB activation downstream of GITR depends on a previously mapped TRAF-binding site in the cytoplasmic domain of the receptor and is inhibited by the cytoplasmic protein A20. GITR is thought to inhibit the suppressive function of regulatory T cells (Treg cells) and to promote activation of T cells. Taken together, our studies provide the first indications that TRAF4 elaborates GITR signaling and suggest that TRAF4 can modulate the suppressive functions of Treg cells.

Key words.

TNFR-associated factor (TRAF) glucocorticoid-induced TNFR (GITR) signal transduction nuclear factor κB (NF-κB) 


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Copyright information

© Birkhäuser Verlag, Basel 2004

Authors and Affiliations

  1. 1.School of Medicine, Departments of Medicine and Pathology and ImmunologyWashington UniversitySaint LouisUSA

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