title: A novel protein modification pathway related to the ubiquitin system.
abstract: 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.
authors.affiliation: ZMBH, Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Liakopoulos
authors.forename: G
authors.initials: G
authors.lastname: Doenges
authors.forename: K
authors.initials: K
authors.lastname: Matuschewski
authors.forename: S
authors.initials: S
authors.lastname: Jentsch
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D044842:Cullin Proteins; D018076:DNA, Complementary; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D044764:Ubiquitin-Activating Enzymes; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D018076:DNA, Complementary; D005656:Fungal Proteins; C111706:RUB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C112594:UBA3 protein, S cerevisiae; C112595:UBC12 protein, S cerevisiae; C112593:ULA1 protein, S cerevisiae; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D044764:Ubiquitin-Activating Enzymes