MARCH ligases in immunity

Haiyin Liu; Justine D Mintern; Jose A Villadangos

doi:10.1016/j.coi.2019.03.001

MARCH ligases in immunity

Curr Opin Immunol. 2019 Jun:58:38-43. doi: 10.1016/j.coi.2019.03.001. Epub 2019 May 4.

Authors

Haiyin Liu¹, Justine D Mintern², Jose A Villadangos³

Affiliations

¹ The Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.
² The Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: jmintern@unimelb.edu.au.
³ The Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia; The Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. Electronic address: j.villadangos@unimelb.edu.au.

PMID: 31063934
DOI: 10.1016/j.coi.2019.03.001

Abstract

Membrane associated RING-CH (MARCH) ubiquitin ligases control the stability, trafficking and function of important immunoreceptors, including MHC molecules and costimulatory molecule CD86. Regulation of the critical antigen presenting molecule MHC II by MARCH1 and the control of MARCH1 expression by inflammatory stimuli is a key step in the function of antigen presenting cells. MHC II ubiquitination by MARCH8 and CD83 plays a critical role in T cell thymic selection. Recent studies reveal new immune functions of MARCH ligases in innate immunity, regulation of FcγR expression and T_reg development. In addition, we review the importance of MARCH in immunomodulation at the host-pathogen interface. Both bacterial and viral pathogens manipulate MARCH function, while MARCH ligases act as an important host anti-viral defence mechanism. Here, we review the role of membrane-bound MARCH ligases in immune function and provide an update on new substrates and concepts. Understanding the increasingly complex roles of MARCH E3 ligases will be vital to develop therapeutic strategies for their regulation.

Publication types

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

MeSH terms

Animals
Antigens, CD / immunology*
Antigens, CD / metabolism
CD83 Antigen
Histocompatibility Antigens Class II / immunology*
Histocompatibility Antigens Class II / metabolism
Humans
Immunity, Innate / immunology
Immunoglobulins / immunology*
Immunoglobulins / metabolism
Membrane Glycoproteins / immunology*
Membrane Glycoproteins / metabolism
Receptors, IgG / immunology
Receptors, IgG / metabolism
T-Lymphocytes / immunology*
T-Lymphocytes, Regulatory / immunology
T-Lymphocytes, Regulatory / metabolism
Ubiquitin-Protein Ligases / immunology*
Ubiquitin-Protein Ligases / metabolism
Ubiquitination / immunology*

Substances

Antigens, CD
Histocompatibility Antigens Class II
Immunoglobulins
Membrane Glycoproteins
Receptors, IgG
MARCHF8 protein, human
Ubiquitin-Protein Ligases