Proteomic analyses reveal that immune integrins are major targets for regulation by Membrane-Associated Ring-CH (MARCH) proteins MARCH2,3,4 and 9
- Sandow, JJ; Webb, AI; Stockwell, D; Kershaw, NJ; Tan, C; Ishido, S; Alexander, WS; Hilton, DJ; Babon, JJ; Nicola, NA;
Publication Year 2021-05-04, Volume 21, Issue #11-12, Page e2000244
- Journal Title
- 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 (IL6Rα). Here we use 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 cell surface proteins regulated by more than one MARCH protein in addition to several MARCH protein-specific cell surface targets 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 α4β1 (VLA4 or VCAM-1 receptor) was down-regulated only by MARCH2 and we showed that in MARCH2 knockout mice, Integrin α4 was up-regulated specifically in mature B-lymphocytes and this was accompanied by decreased numbers of B-cells in the spleen. This article is protected by copyright. All rights reserved.
- B-cells; Integrins; March; cell surface
- WEHI Research Division(s)
- Advanced Technology And Biology; Blood Cells And Blood Cancer; Personalised Oncology; Structural Biology
- PubMed ID
- Publisher's Version
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- Refer to copyright notice on published article.
Creation Date: 2021-05-11 04:12:15Last Modified: 2021-07-07 11:09:27