PXD053722 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-07-07 06:03:10 | ID requested | |
⏵ 1 | 2024-08-28 08:04:49 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: SDH deficiency |
Succinate |
Drug resistance |
UBC12 phosphorylation |
Acute myeloid leukemia |
Contact List
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 | |
Full Dataset Link List
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 |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD053722
- Label: PRIDE project
- Name: SDH deficiency-driven succinate accumulation dictates the drug resistance of AML through regulating p-UBC12/cullin activity