PXD067362

PXD067362 is an original dataset announced via ProteomeXchange.

Title	Unc-51 Like Kinase 3 (ULK3) is essential for autophagy and cell survival in multiple myeloma
Description	Despite the availability of effective therapies such as proteasome inhibitors, multiple myeloma (MM) patients relapse with refractory disease. To identify new therapeutic targets, we assessed RNA sequencing data from CD138+ MM patient cells (n = 813) across disease stages and found that an autophagy gene signature, and particularly ULK3 expression, was strongly associated with disease progression. Functional studies revealed that ULK3 contributes to MM cell survival as part of the ULK-ATG13-FIP200 complex. We generated inhibitors (SG3-014/MA9-060) with nanomolar potency and confirmed their binding mode through co-crystallization with ULK3. In vivo, ULK3 inhibition reduced MM burden, improved survival, and protected against cancer-induced bone disease. MA9-060 also restored sensitivity to proteasome inhibitors in resistant MM cells. This synergy was validated ex vivo in patient samples, especially those with high ULK3 expression. These findings indicate a new role for ULK3-mediated autophagy in cancer and suggest that ULK3 inhibition is an effective treatment strategy for both newly diagnosed and refractory MM disease.
HostingRepository	PRIDE
AnnounceDate	2026-05-27
AnnouncementXML	Submission_2026-05-27_12:45:58.046.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD067362
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-14 15:01:00	ID requested
⏵ 1	2026-05-27 12:45:58	announced

10.6019/PXD067362;

submitter keyword: Autophagy, ULK3, Interactome,Multiple Myeloma

Conor Lynch
contact affiliation	Tumor Microenvironment & Metastasis Department Cancer Biology & Evolution Program Moffitt Cancer Center Tampa, FL, USA
contact email	conor.lynch@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067362
     1. Label: PRIDE project
     2. Name: Unc-51 Like Kinase 3 (ULK3) is essential for autophagy and cell survival in multiple myeloma