Dataset Information

Proteomic analyses reveal that immune integrins are major targets for proteolysis by Membrane-Associated Ring-CH (MARCH) proteins MARCH2, 3, 4 and 9.

ABSTRACT: MARCH proteins are membrane-associated Ring-CH E3 ubiquitin ligases that dampen immune responses by down-regulating cell surface expression of major histocompatibility complexes I and II as well as immune co-stimulatory receptors. We recently showed that MARCH2,3,4 and 9 also down-regulate cell surface expression of the inflammatory cytokine receptor for interleukin-6 (IL6Ra). We used over-expression of these MARCH proteins in the M1 myeloid leukemia cell line and cell surface proteomic analyses to globally analyse other potential targets of these proteins. A large range of overlapping and a few unique cell surface proteins were identified most of which were down-regulated by MARCH expression. Prominent amongst these were several integrin complexes associated with immune cell homing, adhesion and migration. Integrin 41 (VLA4 or VCAM-1 receptor) was down-regulated only by MARCH2 and we showed that in MARCH2 knockout mice Integrin 4 was up-regulated specifically in mature B-lymphocytes and this was accompanied by decreased numbers of B-cells in the spleen.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Cell, Blood

SUBMITTER: Jarrod Sandow

LAB HEAD: Nicos A Nicola

PROVIDER: PXD019967 | Pride | 2021-05-07

REPOSITORIES: Pride

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Proteomic analyses reveal that immune integrins are major targets for regulation by Membrane-Associated Ring-CH (MARCH) proteins MARCH2, 3, 4 and 9.

Sandow Jarrod J JJ Webb Andrew I AI Stockwell Dina D Kershaw Nadia J NJ Tan Cyrus C Ishido Satoshi S Alexander Warren S WS Hilton Douglas J DJ Babon Jeffrey J JJ Nicola Nicos A NA

Proteomics 20210519 11-12

MARCH proteins are membrane-associated Ring-CH E3 ubiquitin ligases that dampen immune responses by downregulating cell surface expression of major histocompatibility complexes I and II as well as immune co-stimulatory receptors. We recently showed that MARCH2,3,4 and 9 also downregulate cell surface expression of the inflammatory cytokine receptor for interleukin-6 (IL6Rα). Here we use over-expression of these MARCH proteins in the M1 myeloid leukaemia cell line and cell surface proteomic analy ...[more]

PMID: 33945654

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