title: Interaction of U-box-type ubiquitin-protein ligases (E3s) with molecular chaperones.
abstract: Members of the U-box family of proteins constitute a class of ubiquitin-protein ligases (E3s) distinct from the HECT-type and RING finger-containing E3 families. Two representative mammalian U-box proteins, UFD2a and CHIP, interact with the molecular chaperones VCP and either Hsp90 or Hsc70, respectively, and are implicated in the degradation of damaged proteins. We have now investigated the roles of mammalian U-box proteins by performing a comprehensive screen for molecules that interact with these proteins in the yeast two-hybrid system. All mammalian U-box proteins tested were found to interact with molecular chaperones or cochaperones, including Hsp90, Hsp70, DnaJc7, EKN1, CRN, and VCP. These observations suggest that the function of U box-type E3s is to mediate the degradation of unfolded or misfolded proteins in conjunction with molecular chaperones as receptors that recognize such 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.
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yada
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004926:Escherichia coli / Q000235:genetics; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D011506:Proteins; D011994:Recombinant Proteins; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D005982:Glutathione Transferase; D001616:beta-Galactosidase; D008025:Ligases