Ubiquitin conjugating enzymes participate in polyglutamine protein aggregation

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dc.contributor.authorHoward, Rebecca A.
dc.contributor.authorSharma, Pratima
dc.contributor.authorHajjar, Connie
dc.contributor.authorCaldwell, Kim A.
dc.contributor.authorCaldwell, Guy A.
dc.contributor.authorDu Breuil, Rusla
dc.contributor.authorMoore, Rhonda
dc.contributor.authorBoyd, Lynn
dc.contributor.otherUniversity of Alabama Huntsville
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.date.accessioned2023-10-02T15:18:25Z
dc.date.available2023-10-02T15:18:25Z
dc.date.issued2007
dc.description.abstractBackground: Protein aggregation is a hallmark of several neurodegenerative diseases including Huntington's disease and Parkinson's disease. Proteins containing long, homopolymeric stretches of glutamine are especially prone to form aggregates. It has long been known that the small protein modifier, ubiquitin, localizes to these aggregates. In this report, nematode and cell culture models for polyglutamine aggregation are used to investigate the role of the ubiquitin pathway in protein aggregation. Results: Ubiquitin conjugating enzymes (Ubc's) were identified that affect polyglutamine aggregates in C. elegans. Specifically, RNAi knockdown of ubc-2 or ubc-22 causes a significant increase in the size of aggregates as well as a reduction in aggregate number. In contrast, RNAi of ubc-1, ubc-13, or uev-1 leads to a reduction of aggregate size and eliminates ubiquitin and proteasome localization to aggregates. In cultured human cells, shRNA knockdown of human homologs of these Ubc's (Ube2A, UbcH5b, and E2- 25K) causes similar effects indicating a conserved role for ubiquitination in polyglutamine protein aggregation. Conclusion: Results of knockdown of different Ubc enzymes indicate that at least two different and opposing ubiquitination events occur during polyglutamine aggregation. The loss of ubiquitin localization after ubc-1, ubc-13, or uev-1 knockdown suggests that these enzymes might be directly involved in ubiquitination of aggregating proteins.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationHoward, R. A., Sharma, P., Hajjar, C., Caldwell, K. A., Caldwell, G. A., du Breuil, R., Moore, R., & Boyd, L. (2007). Ubiquitin conjugating enzymes participate in polyglutamine protein aggregation. In BMC Cell Biology (Vol. 8, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/1471-2121-8-32
dc.identifier.doi10.1186/1471-2121-8-32
dc.identifier.orcidhttps://orcid.org/0000-0002-9860-6830
dc.identifier.orcidhttps://orcid.org/0000-0002-8283-9090
dc.identifier.orcidhttps://orcid.org/0000-0003-1580-6122
dc.identifier.orcidhttps://orcid.org/0000-0002-2951-2873
dc.identifier.urihttps://ir.ua.edu/handle/123456789/12622
dc.languageEnglish
dc.language.isoen_US
dc.publisherBMC
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCAENORHABDITIS-ELEGANS
dc.subjectINTRANUCLEAR INCLUSIONS
dc.subjectPROTEASOME SYSTEM
dc.subjectALPHA-SYNUCLEIN
dc.subjectPOLYUBIQUITIN
dc.subjectDEGRADATION
dc.subjectINTERFERENCE
dc.subjectDYSFUNCTION
dc.subjectPATHWAY
dc.subjectMICE
dc.subjectCell Biology
dc.titleUbiquitin conjugating enzymes participate in polyglutamine protein aggregationen_US
dc.typeArticle
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