Journal article
The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation
Z Kuang, RS Lewis, JM Curtis, Y Zhan, BM Saunders, JJ Babon, TB Kolesnik, A Low, SL Masters, TA Willson, L Kedzierski, S Yao, E Handman, RS Norton, SE Nicholson
Journal of Cell Biology | Published : 2010
Abstract
Inducible nitric oxide (NO) synthase (iNOS; NOS2) produces NO and related reactive nitrogen species, which are critical effectors of the innate host response and are required for the intracellular killing of pathogens such as Mycobacterium tuberculosis and Leishmania major. We have identified SPRY domain-containing SOCS (suppressor of cytokine signaling) box protein 2 (SPSB2) as a novel negative regulator that recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in its proteasomal degradation. SPSB2 interacts with the N-terminal region of iNOS via a binding interface on SPSB2 that has been mapped by nuclear magnetic resonance spectroscopy and mutational analyses. SPSB2..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported in part by the National Health and Medical Research Council, Australia (Program grant 461219 and Project grant 461233 to R. S. Norton and S. E. Nicholson, fellowships to R. S. Norton and S. E. Nicholson, and Independent Research Institutes Infrastructure Support Scheme grant 361646) as well as a Victorian State Government operational infrastructure support grant.