Regulation of T cell development by the deubiquitinating enzyme CYLD

William Reiley, Minying Zhang, Wei Jin, Mandy Losiewicz, Keri B. Donohue, Christopher C. Norbury, Shao Cong Sun

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

T cell receptor signaling is essential for the generation and maturation of T lymphocyte precursors. Here we identify the deubiquitinating enzyme CYLD as a positive regulator of proximal T cell receptor signaling in thymocytes. CYLD physically interacted with active Lck and promoted recruitment of active Lck to its substrate, Zap70. CYLD also removed both Lys 48- and Lys 63-linked polyubiquitin chains from Lck. Because of a cell-autonomous defect in T cell development, CYLD-deficient mice had substantially fewer mature CD4+ and CD8+ single-positive thymocytes and peripheral T cells.

Original languageEnglish (US)
Pages (from-to)411-417
Number of pages7
JournalNature Immunology
Volume7
Issue number4
DOIs
StatePublished - Apr 2006

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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