PXD023372

PXD023372 is an original dataset announced via ProteomeXchange.

Title	Endogenous anti-tumorigenic nitro-fatty acids potently suppress the ubiquitin-proteasome system
Description	Nitro-fatty acids (NFAs) are endogenously formed lipid mediators that cause a broad spectrum of anti-inflammatory effects by covalent modification of key proteins within inflammatory signaling pathways. Their potential as therapeutics has been demonstrated in numerous animal models of disease. Herein, we evaluated the anti-tumorigenic effects of NFAs in the colon carcinoma cell line Caco-2 and other solid and leukemic tumor cell lines. NFAs inhibited the ubiquitin–proteasome system (UPS), leading to polyubiquitination and inhibition of the proteasome activities. Suppression of the UPS induced the pro-apoptotic transcription factor CHOP by activation of the unfolded protein response (UPR), resulting in tumor cell death. NFA-mediated effects on UPS and UPR were rather strong, highly specific, largely irreversible, and represent a mechanistically new mode of action for pharmacological suppression of the UPS. Taking into account their favorable safety profile in clinical phase I trials in combination with their well-recognized anti-tumorigenic efficacy covering solid tumors, we conclude that NFAs are innovative proteasome inhibitor drug candidates that may have a large potential to overcome the limitations of the classical proteasome inhibitors.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:34:39.304.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shady Amr
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	2021-01-04 02:25:03	ID requested
1	2024-03-26 06:43:11	announced
⏵ 2	2024-10-22 06:34:39	announced	2024-10-22: Updated project metadata.

10.1016/J.CHEMBIOL.2023.06.017;

submitter keyword: apoptosis/ cancer/ lipid mediators/ polyubiquitination/ unfolded protein response

Dr. Christian Münch
contact affiliation	Institute of Biochemistry II - Goethe-Universität Frankfurt am Main
contact email	ch.muench@em.uni-frankfurt.de
lab head
Shady Amr
contact affiliation	Institute of Biochemistry II - Goethe-Universität Frankfurt am Main
contact email	amr@med.uni-frankfurt.de
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/2024/03/PXD023372

PRIDE project URI

• PRIDE
  1. PXD023372
     1. Label: PRIDE project
     2. Name: Endogenous anti-tumorigenic nitro-fatty acids potently suppress the ubiquitin-proteasome system