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PXD019553 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSite-Specific Ubiquitination of Pathogenic Huntingtin Attenuates its Deleterious Effects
DescriptionHuntington’s disease (HD) is a progressive incurable neurodegenerative disorder characterized by motor and neuropsychiatric symptoms. It is caused by expansion of a CAG triplet in the N-terminal domain of exon 1 in the huntingtin (HTT) gene that codes for an expanded polyglutamine (polyQ) stretch in the protein product which becomes aggregation-prone. The mutant Htt (mHtt) aggregates are associated with components of the Ubiquitin-Proteasome System (UPS), suggesting that mHtt is marked for proteasomal degradation and that for reasons still debated are not properly degraded. We used a novel HD rat model, proteomic analysis, and long-term live neuronal imaging to characterize the effects of ubiquitination on aggregation of mHtt and its subsequent cellular response. We identified two lysine residues - 6 and 9 - in the first exon of mHtt that are specifically ubiquitinated in striatal and cortical brain tissues of mHtt-transgenic animals. Expression of mHtt exon 1 lacking these ubiquitination sites in cortical neurons and cultured cells was found to slow aggregate appearance rates and reduce their size, but at the same time increase the number of much smaller and less visible ones. Importantly, expression of this form of mHtt was associated with elevated death rates. Furthermore, proteomic analysis indicated that compared to cells expressing the protein that can be modified by ubiquitin, cells expressing the lysine-less protein did not activate protein synthetic pathways that enable the cell to cope with stress. Taken together, the findings suggest a novel role for ubiquitination - attenuation of the pathogenic effect of mHtt.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTamar Ziv
SpeciesList scientific name: Rattus rattus (Black rat); NCBI TaxID: 10117;
ModificationListcarbamoylated residue; ubiquitination signature dipeptidyl lysine; monohydroxylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-03 17:14:34ID requested
12020-06-30 04:59:17announced
22020-07-21 18:18:16announced2020-07-22: Updated publication reference for PubMed record(s): 32675242.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Huntingtin Ubiquitination
Contact List
Noam Ziv
contact affiliation1The Rappaport Faculty of Medicine and Research Institute, Haifa 3109601, Israel; 2Network Biology Research Laboratories, Technion-Israel Institute of Technology, Haifa 3200003, Israel
contact emailnoamz@netvision.net.il
lab head
Tamar Ziv
contact affiliationTechnion
contact emailtamarz@tx.technion.ac.il
dataset submitter
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