Editors' ChoiceCell Cycle

NEDD8 Needed for Cell Cycle and Development

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Science's STKE  20 Nov 2001:
Vol. 2001, Issue 109, pp. tw426
DOI: 10.1126/stke.2001.109.tw426

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]