PXD039246

PXD039246 is an original dataset announced via ProteomeXchange.

Title	Repurposing Herpesvirus Protein ORF57 to Inhibit TDP-43 Aggregation
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:53:50.631.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benjamin Wolozin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-04 04:00:48	ID requested
1	2024-08-09 05:06:56	announced
⏵ 2	2024-10-22 06:53:54	announced	2024-10-22: Updated project metadata.

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;

submitter keyword: translational stress response, Alzheimer’s disease, ALS, protein aggregation, TDP-43

Benjamin Wolozin
contact affiliation	Professor, 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 email	bwolozin@bu.edu
lab head
Benjamin Wolozin
contact affiliation	Boston University
contact email	bwolozin@bu.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD039246

PRIDE project URI

• PRIDE
  1. PXD039246
     1. Label: PRIDE project
     2. Name: Repurposing Herpesvirus Protein ORF57 to Inhibit TDP-43 Aggregation