title: U-box proteins as a new family of ubiquitin ligases.
abstract: Ubiquitin-protein ligases (E3s) determine the substrate specificity of ubiquitylation and, until recently, had been classified into two families, the HECT and RING-finger families. The U-box is a domain of approximately 70 amino acids that is present in proteins from yeast to humans. The prototype U-box protein, yeast Ufd2, was identified as a ubiquitin chain assembly factor (E4) that cooperates with a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and an E3 to catalyze the formation of a ubiquitin chain on artificial substrates. We recently showed that mammalian U-box proteins, in conjunction with an E1 and an E2, mediate polyubiquitylation in the absence of a HECT type or RING-finger type E3. U-box proteins have thus been defined as a third family of E3s. We here review recent progress in the characterization of U-box proteins and of their role in the quality control system that underlies the cellular stress response to the intracellular accumulation of abnormal proteins.
authors.affiliation: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan. hatas@bioreg.kyushu-u.ac.jp
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Kei-ichi I
authors.initials: KI
authors.lastname: Nakayama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000502:physiology; D016415:Sequence Alignment; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D018832:Molecular Chaperones; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D008025:Ligases