PXD053722

PXD053722 is an original dataset announced via ProteomeXchange.

Title	SDH deficiency-driven succinate accumulation dictates the drug resistance of AML through regulating p-UBC12/cullin activity
Description	Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct microenvironment-associated metabolic processes. Here, we identified SDH deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to a wide range of anti-cancer therapies. Mechanistically, succinate promoted the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function was mediated by succinate-triggered upregulation of UBC12 phosphorylation, which impaired its E2 function in cullins neddylation. Notably, decreasing succinate levels by fludarabine could effectively restore the drug sensitivity of SDH-deficient AML PDX. Together, we uncover a novel function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.
HostingRepository	PRIDE
AnnounceDate	2024-08-28
AnnouncementXML	Submission_2024-08-28_08:04:48.922.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Meidan Ying
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-07 06:03:10	ID requested
⏵ 1	2024-08-28 08:04:49	announced

Dataset with its publication pending

submitter keyword: SDH deficiency

Succinate

Drug resistance

UBC12 phosphorylation

Acute myeloid leukemia

Meidan Ying
contact affiliation	College of Pharmaceutical Sciences, Zhejiang University
contact email	mying@zju.edu.cn
lab head
Meidan Ying
contact affiliation	Zhejiang University
contact email	mying@zju.edu.cn
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/2024/08/PXD053722

PRIDE project URI

• PRIDE
  1. PXD053722
     1. Label: PRIDE project
     2. Name: SDH deficiency-driven succinate accumulation dictates the drug resistance of AML through regulating p-UBC12/cullin activity