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TRAF2-mediated Lys63-linked ubiquitination of DUSP14/MKP6 is essential for its phosphatase activity

Chia-Yu Yang1, Li-Li Chiu2, Tse-Hua Tan3

  • 1Immunology Research Center, National Health Research Institutes, Zhunan 35053, Taiwan.

Cellular Signalling
|November 2, 2015
PubMed

Insights

Dual-specificity phosphatase 14 (DUSP14) activation in T cells is regulated by ubiquitination. TRAF2-mediated Lys63-linked ubiquitination at lysine 103 activates DUSP14 phosphatase activity during T-cell receptor signaling.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Dual-specificity phosphatase 14 (DUSP14) dephosphorylates MAP kinases and negatively regulates T-cell activation.
  • The precise molecular mechanisms governing DUSP14 activity remain incompletely understood.

Purpose of the Study:

  • To elucidate the post-translational modifications regulating DUSP14 activity.
  • To investigate the role of ubiquitination in DUSP14 function during T-cell receptor signaling.

Main Methods:

  • Mass spectrometry and mutational analyses to identify ubiquitination sites.
  • Co-immunoprecipitation assays to study protein interactions.
  • TRAF2 shRNA knockdown to assess the role of the E3 ligase.

Main Results:

  • DUSP14 undergoes Lys63-linked ubiquitination at lysine 103.
  • TRAF2, an E3 ligase, interacts with DUSP14 during T-cell receptor signaling and mediates its ubiquitination.
  • Ubiquitination of DUSP14 is essential for its phosphatase activity in T cells.

Conclusions:

  • TRAF2-mediated Lys63-linked ubiquitination is a novel mechanism for activating DUSP14.
  • This ubiquitination process plays a critical role in regulating DUSP14 activity during T-cell receptor signaling and immune responses.
Keywords:
DUSP14/MKP6T-cell receptor signalingTRAF2Ubiquitination

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