A novel modification pathway related to the ubiquitin system

ZMBH, Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
The EMBO Journal (Impact Factor: 10.43). 04/1998; 17(8):2208-14. DOI: 10.1093/emboj/17.8.2208
Source: PubMed


Ubiquitin conjugation is known to target protein substrates primarily to degradation by the proteasome or via the endocytic route. Here we describe a novel protein modification pathway in yeast which mediates the conjugation of RUB1, a ubiquitin-like protein displaying 53% amino acid identity to ubiquitin. We show that RUB1 conjugation requires at least three proteins in vivo. ULA1 and UBA3 are related to the N- and C-terminal domains of the E1 ubiquitin-activating enzyme, respectively, and together fulfil E1-like functions for RUB1 activation. RUB1 conjugation also requires UBC12, a protein related to E2 ubiquitin-conjugating enzymes, which functions analogously to E2 enzymes in RUB1-protein conjugate formation. Conjugation of RUB1 is not essential for normal cell growth and appears to be selective for a small set of substrates. Remarkably, CDC53/cullin, a common subunit of the multifunctional SCF ubiquitin ligase, was found to be a major substrate for RUB1 conjugation. This suggests that the RUB1 conjugation pathway is functionally affiliated to the ubiquitin-proteasome system and may play a regulatory role.

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Available from: Kai Matuschewski, Apr 30, 2014
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    • "The neural precursor cell expressed developmentally downregulated-8 pathway and its cross-talk with ubiquitin Neural precursor cell expressed developmentally down- regulated-8 (NEDD8) is a ubiquitin-like molecule (UBL) sharing w60% amino acid identity with ubiquitin. NEDD8 is attached to its substrates in a manner similar to that described for ubiquitination, resulting in the formation of an isopeptide bond linking the terminal carboxyl group of NEDD8 with the 3-amino group of a lysine residue of the substrate (Kumar et al. 1993, Kamitani et al. 1997, Lammer et al. 1998, Liakopoulos et al. 1998, Osaka et al. 1998, Pozo et al. 1998). The NEDDylation enzymatic cascade is composed of the key enzymatic activities named E1, E2, E3 and deconjugating enzymes. "
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    Endocrine Related Cancer 12/2014; 22(1). DOI:10.1530/ERC-14-0315 · 4.81 Impact Factor
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    • "Nedd8 is a ubiquitin-like protein (UBL) that covalently modifies the cullin subunits of the cullin-RING complexes to turn on their activities as E3 ubiquitin (UB) ligases (Figure 1a) [1], [2], [3], [4], [5], [6]. The E1 enzyme specific for Nedd8, also known as Nedd8 activating enzyme (NAE), catalyzes the condensation of ATP with the C-terminal carboxylate of Nedd8 to form a Nedd8-AMP conjugate [5], [7], [8]. The activated Nedd8 is then captured by a catalytic Cys residue of NAE to form a Nedd8∼NAE thioester conjugate (“∼” designates the thioester linkage). "
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    PLoS ONE 08/2013; 8(8):e70312. DOI:10.1371/journal.pone.0070312 · 3.23 Impact Factor
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    • "In the fission yeast Schizosaccharomyces pombe[6,7], as in mammals [8], the null mutation of either Nedd8 itself or components of its conjugation pathway, i.e. its E1 or E2 enzymes, are lethal to the cell. Curiously, the Nedd8 system is not essential for viability of the budding yeast Saccharomyces cerevisiae[9,10]. The reason for this difference is unknown, but could reflect differences in Nedd8 substrates between these organisms. "
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