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Targeting signaling factors for degradation, an emerging mechanism for TRAF functions

Xiao-Dong Yang1, Shao-Cong Sun2,3

  • 1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Immunological Reviews
|June 19, 2015
PubMed

Insights

Tumor necrosis factor receptor-associated factors (TRAFs), particularly TRAF2 and TRAF3, control intracellular signaling by mediating the degradation of key kinases. This ubiquitination system regulates immune and inflammatory responses.

Area of Science:

  • Cellular signaling and immunology
  • Ubiquitination and protein degradation

Background:

  • Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are known signaling adapters.
  • Emerging evidence highlights TRAF2 and TRAF3 roles in regulating intracellular signaling factor fate.
  • TRAF2 and TRAF3 mediate the degradation of nuclear factor-κB (NF-κB)-inducing kinase (NIK).

Purpose of the Study:

  • To review the signaling functions of TRAF proteins in controlling intracellular signaling.
  • To provide historical context and new insights into TRAF-mediated ubiquitination.
  • To explore the role of the cIAP-TRAF2-TRAF3 complex in regulating immune and inflammatory responses.

Main Methods:

  • Literature review of existing studies on TRAF proteins and their signaling functions.
  • Analysis of the ubiquitin-dependent degradation pathways involving TRAF2, TRAF3, and cIAP.
  • Examination of the regulation of the non-canonical NF-κB signaling pathway by TRAF proteins.

Main Results:

  • TRAF2 and TRAF3 form a complex with cIAP (cIAP1 or cIAP2) to target signaling factors for degradation.
  • TRAF3 acts as the NIK-binding adapter in this complex.
  • The cIAP-TRAF2-TRAF3 E3 complex regulates additional signaling factors beyond NIK.
  • This system is crucial for controlling immune and inflammatory responses.

Conclusions:

  • TRAF proteins play a critical role in signal transduction by controlling protein degradation.
  • The ubiquitination system involving cIAP and TRAFs is essential for regulating immune and inflammatory processes.
  • Further research into this ubiquitination system may reveal new therapeutic targets.
Keywords:
NIKTRAF2TRAF3cIAPinflammationnon-canonical NF-κB

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