title: Hereditary spastic paraplegia protein spartin is an FK506-binding protein identified by mRNA display.
abstract: Here, we used mRNA display to search for proteins that bind to FK506, a potent immunosuppressant drug, and identified spartin, a hereditary spastic paraplegia protein, from a human brain cDNA library. We demonstrated that FK506 binds to the C-terminal region of spartin and thereby inhibits the interaction of spartin with TIP47, one of the lipid droplet-associated proteins. We further confirmed that FK506 inhibits localization of spartin and its binder, an E3 ubiquitin ligase AIP4, in lipid droplets and increases the protein level of ADRP (adipose differentiation-related protein), which is a regulator of lipid homeostasis. These results strongly suggest that FK506 suppresses the proteasomal degradation of ADRP, a substrate of AIP4, by inhibiting the spartin-TIP47 interaction and thereby blocking the localization of spartin and AIP4 in lipid droplets.
authors.affiliation: Department of Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Tokunaga
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shiheido
authors.forename: Ichigo
authors.initials: I
authors.lastname: Hayakawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Utsumi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takashima
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Doi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Horisawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakuma-Yonemura
authors.forename: Noriko
authors.initials: N
authors.lastname: Tabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yanagawa
mesh_terms: D018797:Cell Cycle Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016559:Tacrolimus / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D007166:Immunosuppressive Agents; D011506:Proteins; D012333:RNA, Messenger; C464787:SPART protein, human; D016559:Tacrolimus