PXD011359 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The p30 isoform of CEBPA uncovers a silent enhancer to drive the expression of the tumor promoting factor CD73 in CEBPA mutant AML |
Description | The key myeloid transcription factor (TF) CEBPA is frequently mutated in acute myeloid leukemia (AML), but the molecular ramifications of this leukemic driver mutation remain elusive. To investigate CEBPA mutant AML, we compared gene expression changes in human CEBPA mutant AML and in the corresponding CebpaLp30 mouse model, and identified a conserved cross-species transcriptional program. ChIP-seq revealed aberrantly activated enhancers, exclusively occupied by the leukemia-associated CEBPA-p30 isoform. One leukemic-enhancer upstream of Nt5e, encoding CD73, was physically and functionally linked to this conserved AML gene, and could be activated by CEBPA. Targeting of CD73-adenosine signaling increased AML survival in transplanted mice. Our data indicate a first-in-class link between a TF cancer driver mutation and a druggable, direct transcriptional target. |
HostingRepository | PRIDE |
AnnounceDate | 2019-08-08 |
AnnouncementXML | Submission_2019-08-08_07:42:37.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Erwin Schoof |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion ETD |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-10-15 07:35:02 | ID requested | |
⏵ 1 | 2019-08-08 07:42:38 | announced | |
Publication List
Jakobsen JS, Laursen LG, Schuster MB, Pundhir S, Schoof E, Ge Y, d'Altri T, Vitting-Seerup K, Rapin N, Gentil C, Jendholm J, Theilgaard-M, ö, nch K, Reckzeh K, Bullinger L, D, ö, hner K, Hokland P, Fitzgibbon J, Porse BT, Mutant CEBPA directly drives the expression of the targetable tumor-promoting factor CD73 in AML. Sci Adv, 5(7):eaaw4304(2019) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: CEBPA, global proteomics, acute myeloid leukemia |
Contact List
Bo T. Porse |
contact affiliation | 1The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; 2Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark; 3Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, Denmark |
contact email | shb244@ku.dk |
lab head | |
Erwin Schoof |
contact affiliation | Technical University of Denmark |
contact email | erws@dtu.dk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD011359
- Label: PRIDE project
- Name: The p30 isoform of CEBPA uncovers a silent enhancer to drive the expression of the tumor promoting factor CD73 in CEBPA mutant AML