title: TRIM67 protein negatively regulates Ras activity through degradation of 80K-H and induces neuritogenesis.
abstract: Tripartite motif (TRIM)-containing proteins, which are defined by the presence of a common domain structure composed of a RING finger, one or two B-box motifs and a coiled-coil motif, are involved in many biological processes including innate immunity, viral infection, carcinogenesis, and development. Here we show that TRIM67, which has a TRIM motif, an FN3 domain and a SPRY domain, is highly expressed in the cerebellum and that TRIM67 interacts with PRG-1 and 80K-H, which is involved in the Ras-mediated signaling pathway. Ectopic expression of TRIM67 results in degradation of endogenous 80K-H and attenuation of cell proliferation and enhances neuritogenesis in the neuroblastoma cell line N1E-115. Furthermore, morphological and biological changes caused by knockdown of 80K-H are similar to those observed by overexpression of TRIM67. These findings suggest that TRIM67 regulates Ras signaling via degradation of 80K-H, leading to neural differentiation including neuritogenesis.
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yaguchi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Okumura
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Takahashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kameda
authors.forename: Motokazu
authors.initials: M
authors.lastname: Uchigashima
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins; D005786:Gene Expression Regulation; D005959:Glucosidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D009928:Organ Specificity; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011509:Proteoglycans / Q000378:metabolism; D059748:Proteolysis; D000070584:Tripartite Motif Proteins; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination; D033921:Vesicular Transport Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C512949:Prkcsh protein, mouse; D011509:Proteoglycans; C572503:TRIM67 protein, mouse; D000070584:Tripartite Motif Proteins; D033921:Vesicular Transport Proteins; C075430:serglycin; D005959:Glucosidases; D018631:ras Proteins