Ubiquitination signals critical to regulatory T cell development and function

Int Immunopharmacol. 2013 Jul;16(3):348-52. doi: 10.1016/j.intimp.2013.01.023. Epub 2013 Feb 14.

Abstract

Protein ubiquitination has emerged as a crucial modulator of the immune system, participating in the control of T cell differentiation, intracellular signal transduction and the induction of immune tolerance. CD4(+)CD25(+)FOXP3(+) regulatory T cells are a unique subset of cells that mediate central and peripheral immune tolerance. In this review, we highlight our current understanding of the molecular mechanisms and signaling pathways that modulate protein ubiquitination in Treg cells, and how ubiquitination determines Treg cell development and function. Understanding how FOXP3 activity is regulated by ubiquitination and deubiquitination under molecular level will promote regulatory T cell therapy for treating inflammation in autoimmune disease, infection, transplantation and cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Deubiquitinating Enzyme CYLD
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Proto-Oncogene Proteins c-cbl / metabolism
  • Repressor Proteins / metabolism
  • T-Lymphocytes, Regulatory / physiology*
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Adaptor Proteins, Signal Transducing
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • UBE2N protein, human
  • Ubiquitin-Conjugating Enzymes
  • ITCH protein, human
  • CBLB protein, human
  • Proto-Oncogene Proteins c-cbl
  • RNF128 protein, human
  • Ubiquitin-Protein Ligases
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD