Regulation of T Cell Development by the Deubiquitinating Enzyme CYLD

Nat Immunol. 2006 Apr;7(4):411-7. doi: 10.1038/ni1315. Epub 2006 Feb 26.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Crosses, Genetic
  • Immunity, Innate / immunology
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • Tumor Suppressor Proteins / immunology*
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin / immunology
  • Ubiquitin / metabolism
  • ZAP-70 Protein-Tyrosine Kinase / metabolism

Substances

  • Receptors, Antigen, T-Cell
  • Tumor Suppressor Proteins
  • Ubiquitin
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • ZAP-70 Protein-Tyrosine Kinase
  • Zap70 protein, mouse