Regulation of immune system development and function by Cbl-mediated ubiquitination

Immunol Rev. 2019 Sep;291(1):123-133. doi: 10.1111/imr.12789.

Abstract

Ubiquitination is a form of posttranslational protein modification that affects the activity of target proteins by regulating their intracellular degradation, trafficking, localization, and association with other regulators. Recent studies have placed protein ubiquitination as an important regulatory mode to control immune system development, function, and pathogenesis. In this review, we will mainly update the research progress from our laboratory on the roles of the Cbl family of E3 ubiquitin ligases in the development and function of lymphocytes and non-lymphoid cells. In addition, we will highlight our current understanding of the mechanisms used by this family of proteins, especially Cbl and Cbl-b, to co-ordinately regulate the function of various receptors and transcription factors in the context of immune regulation and diseases.

Keywords: Cbl and Cbl-b; T and B cells; germinal center; lymphocyte development; ubiquitination.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Homeostasis
  • Humans
  • Immune System / metabolism*
  • Immune Tolerance
  • Lymphocyte Activation / immunology
  • Organogenesis / immunology*
  • Proto-Oncogene Proteins c-cbl / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Ubiquitination

Substances

  • Adaptor Proteins, Signal Transducing
  • CBLB protein, human
  • Proto-Oncogene Proteins c-cbl

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