TNF Receptor Associated Factors (TRAFs)

Volume 597 of the series Advances in Experimental Medicine and Biology pp 32-47

Physiological Roles and Mechanisms of Signaling by TRAF2 and TRAF5

  • Ping-Yee Billie Au
  • , Wen-Chen YehAffiliated withCampbell Family for Breast Cancer Research, University Health Network and Department of Medical Biophysics, University of Toronto

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TRAF2 and TRAF5 are closely related members of the TRAF family of proteins. They are important signal transducers for a wide range of TNF receptor superfamily members, including TNFR1, TNFR2, CD40 and other lymphocyte costimulatory receptors, RANK/TRANCE-R, EDAR, LTβR, LMP-1 and IRE1. TRAF2 and TRAF5 therefore regulate diverse physiological roles, ranging from T and B cell signaling and inflammatory responses to organogenesis and cell survival. The major pathways mediated by TRAF2 and TRAF5 are the classical and alternative pathways of NF-κB activation, and MAPK and JNK activation. TRAF2 is heavily regulated by ubiquitin signals, and many of the signaling functions of TRAF2 are mediated through its RING domain and likely its own role as an E3 ubiquitin ligase.