Recent advances regarding role of thioredoxin,Txnip, and ARRDC 3 in cancer and other diseases

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  • 癌・病態におけるThioredoxin，Txnip，ARRDC3研究の最近の展開
  • ガン ・ ビョウタイ ニ オケル Thioredoxin, Txnip, ARRDC3 ケンキュウ ノ サイキン ノ テンカイ

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Abstract

<p>　Modification of thiol residues by oxidative stress is an important trigger for biological responses and signal transduction. Thiol residues targeted by oxidative stress are modified either reversibly or irreversibly, depending on the intensity of the stress. In recent years, polysulfide reactions producing S-SH or S-S-SH have become a topic in redox biology. Thioredoxin (TRX) is one of few enzymes that can cleave dithiol bonds of oxidized proteins and polysulfides. In Alzheimer's disease, abnormal proteins can aggregate through interacting thiol residues. Levels of a truncated form of thioredoxin dramatically decrease in individuals with mild cognitive impairment, indicating the importance of thioredoxin research in neurodegenerative disorders. Meanwhile, thioredoxin interacting protein (Txnip), also known as thioredoxin binding protein-2 (TBP-2), is an alpha-arrestin protein that has multiple functions, such as regulating energy metabolism, cancer suppression, and immune function. In particular, Txnip plays a critical role in regulating glucose metabolism by controlling insulin secretion and sensitivity, as well as beta cell apoptosis. We report our findings on thioredoxin-binding protein-2-like inducible membrane protein (TLIMP), another member of the alpha-arrestin subfamily of proteins, also known as arrestin domain containing 3 (ARRDC3). ARRDC3 regulates the beta-adrenergic receptor in collaboration with beta-arrestin. More importantly, ARRDC3 has received increased attention in the cancer research field. Its expression is epigenetically suppressed in basal-like breast cancer patient cells. Single nucleotide polymorphisms located upstream of the ARRDC3 gene have been reported to influence the prognosis of patients with early-onset breast cancer.</p>

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