title: A synthetic defect in protein degradation caused by loss of Ufd4 and Rad23.
abstract: The UFD (ubiquitin fusion degradation) pathway is responsible for multiubiquitination of the fusion proteins that bear a "non-removable" N-terminal ubiquitin moiety. Previous reports have shown that the UFD pathway is conserved from yeast to human. The essential elements of the UFD pathway have also been identified in Saccharomyces cerevisiae. These studies, however, are limited to use of engineered UFD substrates. The biological significance of the UFD pathway remains unknown. Here we demonstrate that Ufd4, the E3 component of the UFD pathway, is involved in controlling the degradation of Rad4, a nucleotide excision repair protein. Moreover, simultaneous loss of Ufd4 and Rad23 exhibits a synthetic inhibitory effect on Rad4 degradation, presenting the first example that a UBA/UBL-domain protein functionally overlaps with a ubiquitin ligase in determining the turnover rate of a protein substrate. The current work also provides a direction for further investigation of the physiological functions of the UFD pathway.
authors.affiliation: Barbara Ann Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine, 110 Warren Ave., Detroit, MI 48201, USA.
authors.forename: Donghong
authors.initials: D
authors.lastname: Ju
authors.forename: Youming
authors.initials: Y
authors.lastname: Xie
mesh_terms: D002172:Canavanine / Q000494:pharmacology; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C490846:RAD23 protein, S cerevisiae; C493797:Rad4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D002172:Canavanine; C509339:Ufd4 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases