PXD037459

PXD037459 is an original dataset announced via ProteomeXchange.

Title	DIA-MS Detect the Dephosphorylation of Tau by Phosphorylation Targeting Chimera (PhosTAC)
Description	Microtubule-associated protein tau is essential for microtubule assembly and stabilization. Hyperphosphorylation of the microtubule-associated protein tau plays an important pathological role in the development of Alzheimer’s disease and other tauopathies, one of the greatest unmet demands in the clinic. In vivo studies using kinase inhibitors suggest that reducing tau phosphorylation levels has therapeutic potential; however, such approaches invariably showed limited benefits. We sought to develop our recently demonstrated Phosphorylation Targeting Chimera (PhosTAC) technology to specifically induce tau dephosphorylation. Herein, we use PhosTACs to recruit tau to PP2A, a native tau phosphatase. PhosTACs induced the formation of a stable ternary complex, leading to a rapid, efficient, and sustained dephosphorylation of tau, which also correlated the enhanced down regulation of tau. Mass spectrometry data validated that PhosTACs downregulated multiple phosphorylation sites of tau. We believe that PhosTACs present advantages over current strategies to modulate tau phosphorylation and represent a new avenue for disease-modifying therapies for tauopathies.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:14.980.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenxue Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-14 14:53:15	ID requested
1	2023-03-15 19:20:11	announced
⏵ 2	2023-11-14 08:44:15	announced	2023-11-14: Updated project metadata.

Hu Z, Chen PH, Li W, Douglas T, Hines J, Liu Y, Crews CM, Targeted Dephosphorylation of Tau by Phosphorylation Targeting Chimeras (PhosTACs) as a Therapeutic Modality. J Am Chem Soc, ():(2023) [pubmed]

submitter keyword: dephosphorylation, DIA-MS,Tau, PhosTAC, phosphoproteomics

Yansheng Liu
contact affiliation	Yale Cancer Biology Institute
contact email	yansheng.liu@yale.edu
lab head
Wenxue Li
contact affiliation	Yale University
contact email	wenxue.li@yale.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/2023/03/PXD037459

PRIDE project URI

• PRIDE
  1. PXD037459
     1. Label: PRIDE project
     2. Name: DIA-MS Detect the Dephosphorylation of Tau by Phosphorylation Targeting Chimera (PhosTAC)