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The E3 Ligase Axotrophin/MARCH-7: Protein Expression Profiling of Human Tissues Reveals Links to Adult Stem Cells
KTH, School of Biotechnology (BIO), Proteomics.ORCID iD: 0000-0001-8993-048X
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2010 (English)In: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 58, no 4, 301-308 p.Article in journal (Refereed) Published
Abstract [en]

Axotrophin/MARCH-7 was first identified in mouse embryonic stem cells as a neural stem cell gene. Using the axotrophin/MARCH-7 null mouse, we discovered profound effects on T lymphocyte responses, including 8-fold hyperproliferation and 5-fold excess release of the stem cell cytokine leukemia inhibitory factor (LIF). Our further discovery that axotrophin/MARCH-7 is required for targeted degradation of the LIF receptor subunit gp190 implies a direct role in the regulation of LIF signaling. Bioinformatics studies revealed a highly conserved RING-CH domain in common with the MARCH family of E3-ubiquitin ligases, and accordingly, axotrophin was renamed "MARCH-7." To probe protein expression of human axotrophin/MARCH-7, we prepared antibodies against different domains of the protein. Each antibody bound its specific target epitope with high affinity, and immunohistochemistry cross-validated target specificity. Forty-eight human tissue types were screened. Epithelial cells stained strongly, with trophoblasts having the greatest staining. In certain tissues, specific cell types were selectively positive, including neurons and neuronal progenitor cells in the hippocampus and cerebellum, endothelial sinusoids of the spleen, megakaryocytes in the bone marrow, crypt stem cells of the small intestine, and alveolar macrophages in the 7 lung. Approximately 20% of central nervous system neuropils were positive. Notably, axotrophin/MARCH-7 has an expression profile that is distinct from that of other MARCH family members. This manuscript contains online supplemental material at http://www.jhc. org. Please visit this article online to view these materials. (J Histochem Cytochem 58:301-308, 2010)

Place, publisher, year, edition, pages
2010. Vol. 58, no 4, 301-308 p.
Keyword [en]
axotrophin/MARCH-7, E3-ligase, LIF, adult stem cells, leukemia-inhibitory-factor, transplantation tolerance, factor lif, t-cells, ubiquitin ligases, down-regulation, in-vitro, generation, system, atlas
National Category
Cell Biology
URN: urn:nbn:se:kth:diva-19342DOI: 10.1369/jhc.2009.954420ISI: 000276006000001ScopusID: 2-s2.0-77949776617OAI: diva2:337389
QC 20110114Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2011-02-14Bibliographically approved

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