PXD012119-1

PXD012119 is an original dataset announced via ProteomeXchange.

Title	PRMT7 substrates .
Description	Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective and cell active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells, is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 resulted in drastically reduced levels of monomethylation of HSP70 family members and other stress-associated proteins. Structural and biochemical analysis revealed that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibited methylation of both, constitutive and inducible forms of HSP70, and led to decreased tolerance for perturbations in proteostasis. These results demonstrate a role for PRMT7 in stress response. SGC3027 is the first chemical probe for PRMT7 and together with its inactive control SGC3027N, will be valuable chemical tools to further investigate the role of PRMT7 in human health and disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_10:21:49.923.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Suzanne Ackloo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-19 03:39:05	ID requested
⏵ 1	2024-10-07 10:21:50	announced

Dataset with its publication pending

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: PRMT7, methylation, epigenetics, SILAC, HSP, substrate

Chery Arrowsmith
contact affiliation	Department of Medical Biophysics, University of Toronto
contact email	cheryl.arrowsmith@uhnresearch.ca
lab head
Suzanne Ackloo
contact affiliation	University of Toronto
contact email	suzanne.ackloo@utoronto.ca
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/2022/02/PXD012119

PRIDE project URI

• PRIDE
  1. PXD012119
     1. Label: PRIDE project
     2. Name: PRMT7 substrates