TRIM67 protein negatively regulates Ras activity through degradation of 80K-H and induces neuritogenesis

J Biol Chem. 2012 Apr 6;287(15):12050-9. doi: 10.1074/jbc.M111.307678. Epub 2012 Feb 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Cytoskeletal Proteins
  • Gene Expression Regulation
  • Glucosidases / genetics
  • Glucosidases / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neurites / metabolism
  • Neurites / physiology*
  • Organ Specificity
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Proteoglycans / metabolism
  • Proteolysis*
  • Tripartite Motif Proteins
  • Two-Hybrid System Techniques
  • Ubiquitination
  • Vesicular Transport Proteins / metabolism
  • ras Proteins / metabolism*

Substances

  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Prkcsh protein, mouse
  • Proteoglycans
  • TRIM67 protein, mouse
  • Tripartite Motif Proteins
  • Vesicular Transport Proteins
  • serglycin
  • Glucosidases
  • ras Proteins