PXD076575-1

PXD076575 is an original dataset announced via ProteomeXchange.

Title	Adipocyte-Derived β-Hydroxybutyrate Confers Metabolic Stress Resistance in Multiple Myeloma
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_02:55:35.540.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	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-03 08:25:52	ID requested
⏵ 1	2026-05-07 02:55:36	announced

Dataset with its publication pending

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

Rui Li
contact affiliation	Thirty Head Street, Yaohai District, Hefei City, Anhui Province, Anhui Medical University East Campus
contact email	18130577714@163.com
lab head
瑞 李
contact affiliation	18130577714
contact email	18130577714@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD076575
     1. Label: PRIDE project
     2. Name: Adipocyte-Derived β-Hydroxybutyrate Confers Metabolic Stress Resistance in Multiple Myeloma