Thioredoxin binding protein (TBP)-2/Txnip and α-arrestin proteins in cancer and diabetes mellitus

  • Masutani Hiroshi
    Institute for Virus Research, Graduate School of Biostudies, Kyoto University
  • Yoshihara Eiji
    Institute for Virus Research, Graduate School of Biostudies, Kyoto University Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University
  • Masaki So
    Institute for Virus Research, Graduate School of Biostudies, Kyoto University
  • Chen Zhe
    Institute for Virus Research, Graduate School of Biostudies, Kyoto University
  • Yodoi Junji
    Institute for Virus Research, Graduate School of Biostudies, Kyoto University

抄録

Thioredoxin binding protein −2/ thioredoxin interacting protein is an α-arrestin protein that has attracted much attention as a multifunctional regulator. Thioredoxin binding protein −2 expression is downregulated in tumor cells and the level of thioredoxin binding protein is correlated with clinical stage of cancer. Mice with mutations or knockout of the thioredoxin binding protein −2 gene are much more susceptible to carcinogenesis than wild-type mice, indicating a role for thioredoxin binding protein −2 in cancer suppression. Studies have also revealed roles for thioredoxin binding protein −2 in metabolic control. Enhancement of thioredoxin binding protein −2 expression causes impairment of insulin sensitivity and glucose-induced insulin secretion, and β-cell apoptosis. These changes are important characteristics of type 2 diabetes mellitus. Thioredoxin binding protein −2 regulates transcription of metabolic regulating genes. Thioredoxin binding protein −2-like inducible membrane protein/ arrestin domain containing 3 regulates endocytosis of receptors such as the β2-adrenergic receptor. The α-arrestin family possesses PPXY motifs and may function as an adaptor/scaffold for NEDD family ubiquitin ligases. Elucidation of the molecular mechanisms of α-arrestin proteins would provide a new pharmacological basis for developing approaches against cancer and type 2 diabetes mellitus.<br>

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