PXD065472

PXD065472 is an original dataset announced via ProteomeXchange.

Title	Adipocyte-Derived β-Hydroxybutyrate Confers Metabolic Stress Resistance in Multiple Myeloma-2
Description	Despite being recognized as a major mesenchymal cell type and a key accomplice in myeloma progression, the precise roles of adipocytes in distinct stages of myeloma pathogenesis remain elusive. Here, we elucidate a critical role of adipocyte-derived β-hydroxybutyrate (β-OHB) in enabling myeloma cells to overcome glucose metabolic stress by sustaining the stability of interferon regulatory factor 4 (IRF4), a master oncoprotein essential for myeloma survival. Under glucose deprivation conditions, AMP-activated protein kinase (AMPK) activation disrupts the IRF4-heat shock protein 90 (HSP90) interaction, enabling the E3 ligase TRIM21-mediated IRF4 ubiquitination and proteasomal degradation. Adipocytes-secreted β-OHB counteracts this process by fueling 3-oxoacid CoA-transferase 1 (OXCT1)-dependent ketolysis and activating N- acetyltransferase 10 (NAT10) to acetylate IRF4 at lysine 87, thereby restoring IRF4-HSP90 binding and blocking TRIM21-mediated IRF4 degradation. Notably, pharmacological inhibition of OXCT1 or NAT10, combined with AMPK activator, synergistically suppresses myeloma growth in vitro and in vivo. Our study thus positions adipocytes-derived β-OHB as a critical metabolic adaptor that empowers myeloma cells to circumvent glucose metabolic stress and highlights a promising therapeutic avenue for targeting metabolic vulnerabilities in multiple myeloma.
HostingRepository	PRIDE
AnnounceDate	2026-05-07
AnnouncementXML	Submission_2026-05-07_03:01:57.399.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	瑞 李
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-25 18:21:30	ID requested
⏵ 1	2026-05-07 03:01:58	announced

Dataset with its publication pending

submitter keyword: IRF4, acetylation,Multiple myeloma, adipocytes, β-hydroxybutyrate

Li Rui
contact affiliation	Anhui Hefei Anhui Medical University
contact email	18130577714@163.com
lab head
瑞 李
contact affiliation	18130577714
contact email	18130577714@163.com
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/2026/05/PXD065472

PRIDE project URI

• PRIDE
  1. PXD065472
     1. Label: PRIDE project
     2. Name: Adipocyte-Derived β-Hydroxybutyrate Confers Metabolic Stress Resistance in Multiple Myeloma-2