PXD042558

PXD042558 is an original dataset announced via ProteomeXchange.

Title	Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterificlation to E2 ubiquitin-conjugating enzymes
Description	UBA1 is the primary E1 ubiquitin-activating enzyme, regulating stability and function of numerous proteins via initiating their ubiquitination. Decreased or insufficient ubiquitination can cause or drive aging and many deadly diseases. Therefore, a small-molecule UBA1 activity enhancer could have broad therapeutic potential. Here we report that auranofin, a drug approved for the treatment of rheumatoid arthritis is a potent UBA1 activity enhancer. Auranofin binds to the UBA1’s ubiquitin fold domain in vitro with a KD of 5.19 nM. The binding enhances UBA1 interactions with at least 20 different E2 ubiquitin-conjugating enzymes, facilitating ubiquitin charging to E2 and increasing the activities of five representative E3s in vitro. Auranofin promotes ubiquitination and degradation of misfolded ER proteins during ER-associated degradation in cells at low nanomolar concentrations. It also facilitates outer mitochondrial membrane-associated degradation. This study discovered the first small-molecule UBA1 activity enhancer, providing a much-needed tool for UBA1 research and therapeutic exploration.
HostingRepository	PRIDE
AnnounceDate	2023-07-10
AnnouncementXML	Submission_2023-07-10_07:39:56.779.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042558
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	DingyinTao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-30 20:38:12	ID requested
⏵ 1	2023-07-10 07:39:57	announced

10.6019/PXD042558;

submitter keyword: Ubiquitination, UBA1,Auranofin

DingyinTao
contact affiliation	National Center for Advancing Translational Sciences, National Institutes of Health
contact email	dingyin.tao@nih.gov
lab head
DingyinTao
contact affiliation	National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS)
contact email	dingyin.tao@nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042558
     1. Label: PRIDE project
     2. Name: Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterificlation to E2 ubiquitin-conjugating enzymes