title: Anchoring of the 26S proteasome to the organellar membrane by FKBP38.
abstract: FK506-binding protein 38 (FKBP38) is a member of the immunophilin family that resides in the mitochondrial outer membrane and the endoplasmic reticulum (ER) membrane. To investigate the physiological function of FKBP38, we performed a comprehensive search for proteins with which it interacts in human cells by liquid chromatographic and mass spectrometric analysis of FKBP38 immunoprecipitates. Almost all subunits of the 26S proteasome were thus found to interact with FKBP38. In vivo co-immunoprecipitation analyses confirmed that FKBP38 indeed associates with the 26S proteasome via its three tandem tetratricopeptide repeats (TPRs). Binding assays in vitro also revealed that FKBP38 directly interacts with the S4 subunit of the 19S proteasome. Immunofluorescence analysis demonstrated that the subcellular distributions of FKBP38 and the 26S proteasome partially overlapped at mitochondria. Both the abundance and activity of the proteasome in a membrane fraction were markedly reduced for mouse embryonic fibroblasts prepared from Fkbp38(-/-) mice compared with those prepared from wild-type mice. These results suggest that FKBP38 functions to anchor the 26S proteasome at the organellar membrane.
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: Tadashi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Michiko
authors.initials: M
authors.lastname: Shirane
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: C471205:FKBP8 protein, human; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D022021:Tacrolimus Binding Proteins