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Neural precursor cell expressed developmentally downregulated 8 (NEDD8); NEDD8 activating enzyme (NAE); ubiquitin-conjugating enzyme E2M (UBE2M; UBC12)

Mouse and cell culture studies suggest inhibiting the NEDD8 signaling pathway could help prevent inflammation. In cell culture, the NAE inhibitor MLN4924 or small hairpin RNA against Ubc12, a component of the NEDD8 pathway, decreased CD4+ T cell activation and proliferation compared with no treatment or control shRNA. In a mouse model of airway inflammation, transfer of T cells with Ubc12 knockdown caused less T cell-mediated lung inflammation than transfer of T cells with no knockdown. Next steps could include evaluating clinical-stage NEDD8 pathway inhibitors in additional inflammation models.
Takeda Pharmaceutical Co. Ltd.'s Millennium Pharmaceuticals Inc. unit has MLN4924 in Phase I testing to treat various cancers.

SciBX 6(3); doi:10.1038/scibx.2013.60
Published online Jan. 24, 2013

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Jin, H.-s. et al. Proc. Natl. Acad. Sci. USA; published online
Dec. 24, 2012;
Contact: Yun-Cai Liu, La Jolla Institute for Allergy & Immunology, La Jolla, Calif.