The molecular mechanism of polyglutamamine-extended proteins to collect ubiquitin receptor proteins was revealed.

On May 30, the international academic journal The FASEB Journal published a research paper on PolyQ-expanded huntingtin and ataxin-3 sequester ubiquitin capors hHR23B and UBQLN2 intos via conjugate dweud ubiquitin.
the study found that polyglutamamine-extended proteins can collect proteins that interact with ubiquitin in cells through their own ubiquitin modifications, causing the function of the collected ubiquitin receptor proteins to impair and cause cytotoxicity.
research supports the group's previously proposed hijacking model, in which protein accumulation raises the important causes of loss of biomolecular function and cytotoxicity in neurodegenerative diseases.
neurodegenerative diseases are a type of disease closely related to protein misfolding and accumulation, including Alzheimer's disease, Parkinson's disease and polyglutamamine-extended diseases.
polyglutamamine (PolyQ) extended disease (PolyQ disease) is caused by a repeat sequence extension of CAG trinucleotides of a specific gene, most commonly including Huntington's disease and spinal cerebellum disorder type 3.
Although the disease's disease-causing proteins vary, a striking common feature of these diseases is the formation of insoluble accumulations or inclusions in specific neurons.
there are many other biomolecules in the inclusion, such as ubiquitin-protease system components, autophagy receptor proteins, molecular mates, and transcription factors, in addition to disease-causing proteins.
interesting, for different neurodegenerative disease-related inclusions, some of the components are unique, while others are the same, such as ubiquitin, protease components, ubiquitin receptor protein hHR23B and UBQLN2 and P97/VCP.
however, it is not known why the inclusions of ubiquitin and ubiquitin-related components are found in the inclusion of proteins associated with different neurodegenerative diseases.
PolyQ-extended protein (yellow) is modified by ubiquitinization (green), the formation of a build-up or inclusion can be modified by unoclide in the cell ubiquitin protein hHR23B and UBQLN2, etc. to collect insoluble accumulation or inclusion, resulting in impaired function of the collected protein.
PolyQ disease is a single gene mutation caused by a single gene mutation, and is a molecular model used to study the pathogenesis of neurodegenerative diseases.
Hu Hongyu research group Yang Hui and Yue Weiwei, with PolyQ extension protein Huntingtin (Htt) and Ataxin-3 (Atx3) as the object of the study of PolyQ extended protein collection cells phenophonin receptor protein hHR23B and UQLBN2 molecular mechanismand cell effects.
they found that PolyQ-extended Htt and Atx3 could especially collect the endogenous receptor proteins hHR23B and UBQLN2 in the cell into insoluble accumulations or inclusions, which depend editing on the unoclus receptor protein hHR23B and UBQLN2 in the ubiquitin binding structure;
they also found that PolyQ-extended Htt and Atx3 in cells reduced the amount of XPC proteins that play an important role in DNA repair by raising hHR23B, suggesting that the collection may cause cytotoxicity by impairing hHR23B function.
the study not only sheds light on the molecular mechanisms of PolyQ extended proteins to collect ubiquitin receptor sins and the formation of ubiquitin-containing inclusions, but also gives researchers a better understanding of the pathogenic molecular mechanisms of PolyQ disease and other neurodegenerative diseases.
the research work has been supported by the Ministry of Science and Technology, the Fund Committee, the Chinese Academy of Sciences and the China Postdoctoral Science Fund.
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