Millions of protein molecules are synthesized per minute in each cell, and simultaneously, millions of protein molecules are degraded. Mutated and misfolded newly synthesized proteins are rapidly degraded to prevent the toxicity caused by the accumulation of these protein fragments. There are two main mechanisms of intracellular protein degradation: the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP). There is a certain relationship between these two mechanisms, and there are some molecules that initiate compensatory effects to prevent disease progression.
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http://dx.doi.org/10.1007/978-981-15-0602-4_25 | DOI Listing |
Zhong 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 PDFBackground: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden.
Background: Alzheimer disease (AD) is a progressive neurodegenerative disease that is accountable for the leading case of dementia in elder people. Before, only symptomatic treatments are available for AD. Since 2021, two anti-amyloid antibodies aducanumab and lecanemab have been approved by the US Food and Drug Administration.
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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