Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders
1Laboratory of Comparative Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu 069-8501, Japan.
International Journal of Molecular Sciences
|February 25, 2023
Summary
Ubiquitin-specific proteases (USPs) play dual roles in metabolic diseases, either improving or worsening conditions like hyperglycemia and non-alcoholic fatty liver disease. Their functions are complex and context-dependent across various tissues.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Ubiquitination and deubiquitination are crucial reversible post-translational modifications impacting protein function.
- Ubiquitin-specific proteases (USPs) are the largest family of deubiquitinating enzymes.
- Emerging evidence links USPs to the pathogenesis and progression of various metabolic disorders.
Purpose of the Study:
- To review the multifaceted roles of USPs in metabolic diseases.
- To elucidate the tissue-specific functions of different USPs in metabolic regulation.
- To summarize current knowledge on USP involvement in hyperglycemia, diabetic complications, and hepatic disorders.
Main Methods:
- Literature review of studies investigating USP functions in metabolic diseases.
- Analysis of experimental data linking USP expression or activity to metabolic phenotypes.
- Synthesis of findings on USP involvement in hyperglycemia, diabetic complications, NAFLD, atherosclerosis, and endocrine disorders.
Main Results:
- Specific USPs (e.g., USP22, USP2, USP9X) show protective effects against hyperglycemia in various cell types and tissues.
- Other USPs (e.g., USP19, USP21) exacerbate hyperglycemia.
- USPs are implicated in diabetic nephropathy, neuropathy, and retinopathy, with varying effects.
- Hepatic USPs have opposing roles in non-alcoholic fatty liver disease (NAFLD).
- USP involvement in atherosclerosis and Cushing syndrome is also highlighted.
Conclusions:
- USPs are critical regulators of energy metabolism with diverse and often opposing roles.
- Tissue-specific functions and context-dependent activities of USPs are key to understanding their impact on metabolic health.
- Further research into USP mechanisms is warranted for therapeutic target identification in metabolic diseases.
Keywords:
atherosclerosiscardiovascular diseasediabetesinsulin resistancemetabolic disordernon-alcoholic fatty liver diseaseobesityubiquitin-specific proteaseMore Related Videos
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