PXD035398

PXD035398 is an original dataset announced via ProteomeXchange.

Title	Diptoindonesin G is a middle domain HSP90 modulator for cancer treatment
Description	HSP90 inhibitors can target many oncoproteins simultaneously, but none have made it through clinical trials due to dose-limiting toxicity and induction of heat shock response, leading to clinical resistance. We identified diptoindonesin G (dip G) as an HSP90 modulator that can promote degradation of HSP90 clients by binding to the middle domain of HSP90 without inducing heat shock response. Although dip G does not bind to the ligand binding domain (LBD) of estrogen receptor (ER), it promotes degradation of ER in breast cancer cells. We further showed that treatment of ER LBD mutantexpressing cells with dip G promoted degradation of wild type and mutant ER with similar efficacy, downregulated ER-regulated gene expression, and inhibited cell proliferation. Our data suggest that dip G circumvents some obstacles associated with HSP90 inhibition and may be developed as a new therapeutic avenue to various cancers, particularly endocrine resistant breast cancer harboring ESR1 mutations
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:29.550.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Min Ma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 00:11:56	ID requested
1	2022-11-16 12:23:37	announced
⏵ 2	2023-11-14 08:57:30	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: ESR1

HSP90

heat shock

LBD mutations

diptoindonesin G

HSP90 inhibitor

Y537S

HSP90 middle domain

ER alpha

Wei Xu
contact affiliation	Marian A. Messerschmidt Professor of Oncology Associate Director, McArdle Laboratory for Cancer Research,UW Madison
contact email	wxu@oncology.wisc.edu
lab head
Min Ma
contact affiliation	UW madison
contact email	mma58@wisc.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/2022/11/PXD035398

PRIDE project URI

• PRIDE
  1. PXD035398
     1. Label: PRIDE project
     2. Name: Diptoindonesin G is a middle domain HSP90 modulator for cancer treatment