NEDD8 Needed for Cell Cycle and Development

Abstract

The function of the posttranslational protein modification termed neddylation, a process whereby NEDD8 monomers (which are very similar to ubiquitin monomers) are covalently attached to proteins, remains largely a mystery. However, neddylation of Cul-1, a member of the Skp1/Cul-1/F-box (SCF) family of proteins, is required for optimum ubiquitylation-dependent protein degradation. Tateishi et al. generated mice deficient in Uba3, which codes for the catalytic activity of the NEDD8-activating enzyme that proteolytically cleaves NEDD8 to a processed form suitable for attachment to proteins. Uba3-deficient mice died in utero, and Uba3 –/– trophoblastic cells were unable to enter S phase during the endoreduplication cycle, a normal process in development by which multiple rounds of S phase occur in the absence of cell division. β-Catenin, a protein in the Wnt signaling pathway, accumulated in the cytoplasm and nuclei of mutant cells, suggesting that the SCF complex and its modification by NEDD8 might have a role in regulating β-catenin degradation. Thus, Uba3-dependent protein neddylation appears to have an important function in cell-cycle control. For more on regulated protein turnover see the STKE Perspective by von Arnim . K. Tateishi, M. Omata, K. Tanaka, T. Chiba, The NEDD8 system is essential for cell cycle progression and morphogenetic pathway in mice. J. Cell Biol. 155 , 571-580 (2001). [Abstract] [Full Text] A. G. von Arnim, A Hitchhiker's Guide to the Proteasome. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/97/pe2 [Summary] [Full Text]