PXD018812

PXD018812 is an original dataset announced via ProteomeXchange.

Title	A cell competition-based drug screen identifies a novel compound that induces dual c-Myc degradation and p53 activation
Description	BCR-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.
HostingRepository	PRIDE
AnnounceDate	2020-12-07
AnnouncementXML	Submission_2020-12-06_23:26:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joseph Robertson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-26 17:22:28	ID requested
⏵ 1	2020-12-06 23:26:49	announced

Dataset with its publication pending

submitter keyword: c-Myc, p53, drug screening, anticancer drug, mRNA, phosphoproteomics, ABL tyrosine kinase, leukemia

Jorrit Enserink
contact affiliation	Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0379 Oslo, Norway
contact email	jorrit.enserink@ibv.uio.no
lab head
Joseph Robertson
contact affiliation	Oslo University Hospital
contact email	joseph.mark.robertson@rr-research.no
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/12/PXD018812

PRIDE project URI

• PRIDE
  1. PXD018812
     1. Label: PRIDE project
     2. Name: A cell competition-based drug screen identifies a novel compound that induces dual c-Myc degradation and p53 activation