Journal article

Membrane-associated RING-CH (MARCH) proteins down-regulate cell surface expression of the interleukin-6 receptor alpha chain (IL6R alpha)

Jeffrey J Babon, Dina Stockwell, Ladina DiRago, Jian-Guo Zhang, Artem Laktyushin, Jose Villadangos, Alan Ching, Satoshi Ishido, Douglas J Hilton, Warren S Alexander, Nicos A Nicola



Interleukin 6 (IL6) is a cytokine that regulates a number of important immune and inflammatory pathways. We used the ability of IL6 to inhibit the clonal proliferation of the mouse M1 myeloid leukemia cell line in agar to positively screen a cDNA expression library for proteins that inhibited IL6 activity. We found three clones completely resistant to IL6 that contained the cDNA for the Membrane-Associated RING-CH E3 ubiquitin ligase MARCH2. MARCH2 is a member of a family of membrane-bound E3 ubiquitin ligases that target cell surface receptors for degradation. MARCH2 overexpressing M1 clones retained responsiveness to the related cytokines leukemia inhibitory factor and oncostatin M and we ..

View full abstract


Awarded by National Health and Medical Research Council of Australia

Awarded by NHMRC IRISS scheme grant

Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council of Australia (Program Grant 1113577, Project Grant 1099752 and Fellowship grants to N.A.N. (1078737), W.S.A. (1058344) and J.J.B. (1121755) as well as infrastructure support from the NHMRC IRISS scheme grant 9000220 and a Victorian State Government Operational Infrastructure Scheme grant.