期刊
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
卷 50, 期 1, 页码 23-34出版社
JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION
DOI: 10.3164/jcbn.11-36SR
关键词
thioredoxin binding protein-2/ thioredoxin interacting protein; thioredoxin binding protein-2-like inducible membrane protein/ arrestin domain containing 3; alpha-arrestin; cancer; diabetes mellitus
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- National Institute of Biomedical Innovation (NIBIO)
- Grants-in-Aid for Scientific Research [23126512] Funding Source: KAKEN
Thioredoxin binding protein -2/ thioredoxin interacting protein is an alpha-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 beta-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 beta(2)-adrenergic receptor. The alpha-arrestin family possesses PPXY motifs and may function as an adaptor/scaffold for NEDD family ubiquitin ligases. Elucidation of the molecular mechanisms of alpha-arrestin proteins would provide a new pharmacological basis for developing approaches against cancer and type 2 diabetes mellitus.
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