PXD040692 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Withanolide analogues disrupt a leukemic dependency on cholesterol transport by inhibiting the oxysterol-binding protein OSBP (TPP) |
Description | Metabolic alterations in cancers precipitate in associated dependencies that can be therapeutically exploited. To meet this goal, natural product inspired small molecules can provide a resource of underexplored chemotypes. We identify W7, a synthetic withanolide analog with pronounced anti-leukemic properties via orthogonal chemical screening. Through multi-omics profiling (including expression proteomics) and genome-scale CRISPR/Cas9 screens, we identify that W7 disrupts Golgi homeostasis via a mechanism that requires active PI4P signaling at the ER-Golgi membrane interface. Thermal proteome profiling and genetic validation studies reveal the oxysterol-binding protein OSBP as the direct and phenotypically relevant target of W7. Collectively, our data reaffirms sterol transport as a therapeutically actionable dependency in leukemia and motivate ensuing translational investigation via the probe-like compound W7. |
HostingRepository | PRIDE |
AnnounceDate | 2024-06-27 |
AnnouncementXML | Submission_2024-06-27_06:07:12.044.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD040692 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Fabian Frommelt |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-03-08 13:13:41 | ID requested | |
⏵ 1 | 2024-06-27 06:07:12 | announced | |
Publication List
10.6019/PXD040692; |
10.1038/s41589-024-01614-4; |
Cigler M, Imrichova H, Frommelt F, Caramelle L, Depta L, Rukavina A, Kagiou C, Hannich JT, Mayor-Ruiz C, Superti-Furga G, Sievers S, Forrester A, Laraia L, Waldmann H, Winter GE, Orpinolide disrupts a leukemic dependency on cholesterol transport by inhibiting OSBP. Nat Chem Biol, ():(2024) [pubmed] |
Keyword List
submitter keyword: thermal proteome profiling, expression proteomics, withanolides,natural product-inspired compound libraries |
Contact List
Dr Georg E. Winter |
contact affiliation | Winter Lab, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences |
contact email | gwinter@cemm.oeaw.ac.at |
lab head | |
Fabian Frommelt |
contact affiliation | CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences |
contact email | fabian.frommelt@hotmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD040692
- Label: PRIDE project
- Name: Withanolide analogues disrupt a leukemic dependency on cholesterol transport by inhibiting the oxysterol-binding protein OSBP (TPP)