SHARPIN acts independently of the ubiquitin-assembly complex LUBAC to attenuate proximal signaling downstream of TCRs by inhibiting the interaction of Zap70 with the TCRζ chain through Lys63 (K63)-linked polyubiquitination. SHARPIN deficiency enhanced TCR signaling and impaired the development and function of Treg cells.
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Bowman, M., Pan, F. & Harhaj, E. SHARPINing the knowledge of TCR signal control. Nat Immunol 17, 221–222 (2016). https://doi.org/10.1038/ni.3387
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DOI: https://doi.org/10.1038/ni.3387
