The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation
AuthorKuang, Z; Lewis, RS; Curtis, JM; Zhan, Y; Saunders, BM; Babon, JJ; Kolesnik, TB; Low, A; Masters, SL; Willson, TA; ...
Source TitleThe Journal of Cell Biology
PublisherROCKEFELLER UNIV PRESS
University of Melbourne Author/sNicholson, Sandra; Yao, Shenggen; Babon, Jeffrey; Masters, Seth; Kedzierski, Lukasz
AffiliationMedical Biology (W.E.H.I.)
Veterinary and Agricultural Sciences
Document TypeJournal Article
CitationsKuang, Z., Lewis, R. S., Curtis, J. M., Zhan, Y., Saunders, B. M., Babon, J. J., Kolesnik, T. B., Low, A., Masters, S. L., Willson, T. A., Kedzierski, L., Yao, S., Handman, E., Norton, R. S. & Nicholson, S. E. (2010). The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation. JOURNAL OF CELL BIOLOGY, 190 (1), pp.129-141. https://doi.org/10.1083/jcb.200912087.
Access StatusOpen Access
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-deficient macrophages showed prolonged iNOS expression, resulting in a corresponding increase in NO production and enhanced killing of L. major parasites. These results lay the foundation for the development of small molecule inhibitors that could disrupt the SPSB-iNOS interaction and thus prolong the intracellular lifetime of iNOS, which may be beneficial in chronic and persistent infections.
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References