Sarcopenia is characterized by reduced muscle strength and mass and a decline in muscle fiber diameter and amount of sarcomeric proteins. Sarcopenia involves the activation of the ubiquitin-proteasome system (UPS). MuRF-1 and atrogin-1 are E3 ubiquitin ligases belonging to UPS, leading to proteolysis mediated by the PSMB 5, 6, and 7 subunits of 20S proteasome. CCL5/RANTES induces a sarcopenic-like effect in muscle cells. The present work explored the impact of CCL5 on UPS components and the influence of UPS on its sarcopenic-like effect. We demonstrated that CCL5 increased MuRF-1 and atrogin-1 protein levels and mRNA levels of subunits PSMB 5, 6, and 7. We used the MG132 inhibitor to elucidate the role of the 20S proteasome in the CCL5-induced sarcopenic-like effect. This inhibitor prevented the decrease in troponin and MHC protein levels and partially prevented the reduction in the diameter of single-isolated FDB muscle fibers induced by CCL5. These findings indicate that CCL5 actively modulates the UPS. Moreover, our results show the direct participation of UPS in the sarcopenic-like phenotype induced by CCL5.
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http://dx.doi.org/10.4081/ejtm.2024.12249 | DOI Listing |
Int J Mol Sci
December 2024
Research Center for High Altitude Medicine, Qinghai University, Xining 810001, China.
Osteoporosis, a prevalent metabolic bone disorder, is characterized by reduced bone density and increased fracture risk. The pathogenesis of osteoporosis is closely associated with an imbalance in bone remodeling, in which the resorption function of osteoclasts exceeds the formation function of osteoblasts. Hypoxia has been implicated in the promotion of osteoclast differentiation and the subsequent development of osteoporosis.
View Article and Find Full Text PDFCells
December 2024
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China.
Ubiquitin-conjugating enzyme E2 T (UBE2T) is a crucial E2 enzyme in the ubiquitin-proteasome system (UPS), playing a significant role in the ubiquitination of proteins and influencing a wide range of cellular processes, including proliferation, differentiation, apoptosis, invasion, and metabolism. Its overexpression has been implicated in various malignancies, such as lung adenocarcinoma, gastric cancer, pancreatic cancer, liver cancer, and ovarian cancer, where it correlates strongly with disease progression. UBE2T facilitates tumorigenesis and malignant behaviors by mediating essential functions such as DNA repair, apoptosis, cell cycle regulation, and the activation of oncogenic signaling pathways.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
August 2024
School of Economics and Management, Beijing Forestry University, Beijing 100083, China.
OTU domain-containing protein 3 (OTUD3) is a crucial deubiquitinase that exhibits significant expression differences across various disease models. OTUD3 plays a role in regulating biological functions such as apoptosis, inflammatory responses, cell cycle, proliferation, and invasion in different cell types. By deubiquitinating key substrate proteins, OTUD3 is involved in essential physiological and pathological processes, including innate antiviral immunity, neural development, neurodegenerative diseases, and cancer.
View Article and Find Full Text PDFJ Cancer
January 2025
The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
The ubiquitin-proteasome system influences cancer progression through multiple mechanisms. Due to the extensive proteasomal modifications observed in cancer tissues, ubiquitination is closely related to various biological functions with cancer. However, the roles of ubiquitin-related genes (UbRGs) in breast cancer (BC) have not been thoroughly investigated.
View Article and Find Full Text PDFSheng Li Xue Bao
December 2024
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou 325000, China.
The N-end rule pathway is a protein degradation pathway mediated by the ubiquitin-proteasome system, which specifically targets and degrades target proteins by recognizing specific residues at the N-terminus of the proteins. The residues which play a crucial role in the N-end rule pathway are called degrons, also known as N-degrons, as they are usually unstable at the N-terminal end of the protein. Currently, several N-end rule pathways have been identified in the eukaryotes, including the Arg/N-end rule, Ac/N-end rule, and Pro/N-end rule pathways, as well as the recently discovered Gly/N-end rule pathway.
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