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PXD048252

PXD048252 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFunctional Role of Fatty Acid Synthase for Signal Transduction in Core-Binding Factor Acute Myeloid Leukemia with an Activating c-Kit Mutation
DescriptionAcute myeloid leukemia (AML) is a rare hematological malignancy with a poor prog-nosis. Activating c-Kit (CD117) mutations occur in 5% of de novo AML and 30% of core-binding factor (CBF) AML, leading to worse clinical outcomes. Posttranslational modifications, particularly with myristic and palmitic acid, are crucial for various cellular processes, including membrane organization, signal transduction, and apoptosis regu-lation. However, most research has focused on solid tumors, with limited understanding of these mechanisms in AML. Fatty acid synthase (FASN), a key palmito-yl-acyltransferase, regulates the subcellular localization, trafficking, and degradation of target proteins, such as H-Ras, N-Ras, and FLT3-ITDmut receptors in AML. Methods: In this study, we investigated the role of FASN in two c-Kit-N822K-mutated AML cell lines using FASN knockdown via shRNA and the FASN inhibitor TVB-3166. Functional im-plications, including cell proliferation, were assessed through Western blotting, mass spectrometry, and PamGene. Results: FASN inhibition led to an increased phosphory-lation of c-Kit (p-c-Kit), Lyn kinase (pLyn), MAP kinase (pMAPK), and S6 kinase (pS6). Furthermore, we observed sustained high expression of Gli1 in Kasumi1 cells following FASN inhibition, which is well known to be mediated by the upregulation of pS6. Conclusions: The combination of TVB-3166 and the Gli inhibitor GANT61 resulted in a significant reduction in the survival of Kasumi1 cells.
HostingRepositoryPRIDE
AnnounceDate2025-03-05
AnnouncementXMLSubmission_2025-03-05_02:38:45.820.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBente Siebels
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-04 06:57:00ID requested
12025-03-05 02:38:46announced
Publication List
10.3390/BIOMEDICINES13030619;
Keyword List
submitter keyword: Akt, VPS45, Gli1, palmitoylation, Lyn, AML, hedgehog signaling, TVB3166,fatty acid synthase, S6 kinase, PI3K, c-Kit mutation, mTOR
Contact List
Dr. Maxim
contact affiliationUniversity Medical Center Schleswig-Holstein, Clinic for Hematology and Oncology,Lübeck, Germany
contact emailMaxim.Kebenko@uksh.de
lab head
Bente Siebels
contact affiliationSection for Mass spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf
contact emailb.siebels@uke.de
dataset submitter
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