title: A conserved island of BAG6/Scythe is related to ubiquitin domains and participates in short hydrophobicity recognition.
abstract: BAG6 (also called Scythe) interacts with the exposed hydrophobic regions of newly synthesized proteins and escorts them to the degradation machinery through mechanisms that remain to be elucidated. In this study, we provide evidence that BAG6 physically interacts with the model defective protein substrate CL1 in a manner that depends directly on its short hydrophobicity. We found that the N terminus of BAG6 contains an evolutionarily conserved island tentatively designated the BAG6 ubiquitin-linked domain. Partial deletion of this domain in the BAG6 N-terminal fragment abolished in cell recognition of polyubiquitinated polypeptides as well as the hydrophobicity-mediated recognition of the CL1 degron in cell and in vitro. These observations suggest a mechanism whereby the BAG6 ubiquitin-linked domain provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.|Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Minami
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yanagi
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Hayashishita
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Rigel
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Yokota
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.|Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, Japan.
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Structural Biology Research Center, Photon Factory, IMSS, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kuwabara
authors.affiliation: Structural Biology Research Center, Photon Factory, IMSS, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kato
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawahara
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C116358:BAG6 protein, Xenopus; C092009:BAG6 protein, human; C484266:Bag6 protein, mouse; D002352:Carrier Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D025801:Ubiquitin; D029867:Xenopus Proteins
keywords: 26S proteasome; BAT3; CL1 degron; protein quality control; ubiquitin