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PXD018812-1

PXD018812 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA cell competition-based drug screen identifies a novel compound that induces dual c-Myc degradation and p53 activation
DescriptionBCR-Abl is a driver oncogene that causes chronic myeloid leukemia and a subset of acute lymphoid leukemias. Although tyrosine kinase inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem cells. Leukemic stem cells are cancer-initiating cells that compete with normal hematopoietic stem cells for the bone marrow niche. Using BCR-Abl as a model oncogene, we performed a drug screen based on competition between isogenic untransformed cells and BCR-Abl-transformed cells, and identified several compounds that selectively target BCR-Abl-transformed cells. Systems-level analysis of one of these novel compounds, DJ34, revealed that it induced depletion of c-Myc and activation of p53. c-Myc depletion occurred in a wide range of tumor types, including leukemia, lymphoma, lung, glioblastoma and breast cancer. Further analyses revealed that DJ34 interferes with c-Myc synthesis at the level of transcription, and we provide data showing that DJ34 is a DNA intercalator and topoisomerase II inhibitor. Physiologically, DJ34 induced apoptosis, cell cycle arrest and cell differentiation, and primary leukemic stem cells were particularly sensitive to DJ34. Taken together, we have identified a novel compound that dually targets c-Myc and p53 in a wide variety of cancers, and with particularly strong activity against leukemic stem cells.
HostingRepositoryPRIDE
AnnounceDate2020-12-07
AnnouncementXMLSubmission_2020-12-06_23:26:48.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJoseph Robertson
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-26 17:22:28ID requested
12020-12-06 23:26:49announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: c-Myc, p53, drug screening, anticancer drug, mRNA, phosphoproteomics, ABL tyrosine kinase, leukemia
Contact List
Jorrit Enserink
contact affiliationDepartment of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0379 Oslo, Norway
contact emailjorrit.enserink@ibv.uio.no
lab head
Joseph Robertson
contact affiliationOslo University Hospital
contact emailjoseph.mark.robertson@rr-research.no
dataset submitter
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Dataset FTP location
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