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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

Abstract.

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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