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PXD039246

PXD039246 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRepurposing Herpesvirus Protein ORF57 to Inhibit TDP-43 Aggregation
DescriptionThe integrated stress response (ISR) is a major element of translation control. The ISR is beneficial in responding to acute stresses, but in human disease a chronic, persistent stress response can contribute to the disease process. Many studies manipulate the ISR by targeting just one protein. However, viral proteins have evolved to target many elements of this system. We examined the Herpesvirus protein ORF57, and determined the protein interaction network and identified that it binds to many proteins linked to the ISR. We show that expressing ORF57 in neuronal SH-SY5Y cells reduces the ISR, inhibiting the accumulation of G3BP1 positive stress granules. We then applied the ORF57 vector to examine the effects on aggregation of TDP-43, which accumulates in neurodegenerative diseases such as amyotrophic lateral sclerosis. We demonstrate that expressing ORF57 changes the dynamics of TDP-43 aggregation and granule formation, reducing the accumulation of aggregated TDP-43 by 36% and increasing the rate of dispersion of TDP-43 aggregates by 2.45-fold. These data suggest that viral proteins, such as ORF57, can be repurposed and applied to inhibit the types of chronic, persistent stress responses in mammalian cells that are associated with neurodegenerative diseases.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:53:50.631.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBenjamin Wolozin
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-01-04 04:00:48ID requested
12024-08-09 05:06:56announced
22024-10-22 06:53:54announced2024-10-22: Updated project metadata.
Publication List
Webber CJ, Murphy CN, Rond, ó, n-Ortiz AN, van der Spek SJF, Kelly EX, Lampl NM, Chiesa G, Khalil AS, Emili A, Wolozin B, Human herpesvirus 8 ORF57 protein is able to reduce TDP-43 pathology: network analysis identifies interacting pathways. Hum Mol Genet, 32(20):2966-2980(2023) [pubmed]
10.1093/hmg/ddad122;
Keyword List
submitter keyword: translational stress response, Alzheimer’s disease, ALS, protein aggregation, TDP-43
Contact List
Benjamin Wolozin
contact affiliationProfessor, Dept. Of Pharmacology and Experimental Therapeutics, Dept. of Neurology, Center for Systems Neuroscience and Center for Neurophotonics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118-2526, USA
contact emailbwolozin@bu.edu
lab head
Benjamin Wolozin
contact affiliationBoston University
contact emailbwolozin@bu.edu
dataset submitter
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