PXD004192-2

PXD004192 is an original dataset announced via ProteomeXchange.

Title	Hoxa9 and Meis1 cooperatively induce addiction to Syk signaling by suppressing miR-146a in acute myeloid leukemia
Description	The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feed-forward loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, we show that Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:29:39.899.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kuan-Ting Pan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-05-20 06:50:41	ID requested
1	2017-06-14 05:23:34	announced
⏵ 2	2024-10-22 04:29:42	announced	2024-10-22: Updated project metadata.

Mohr S, Doebele C, Comoglio F, Berg T, Beck J, Bohnenberger H, Alexe G, Corso J, Str, ö, bel P, Wachter A, Beissbarth T, Schn, ü, tgen F, Cremer A, Haetscher N, G, ö, llner S, Rouhi A, Palmqvist L, Rieger MA, Schroeder T, B, ö, nig H, M, ü, ller-Tidow C, Kuchenbauer F, Sch, ü, tz E, Green AR, Urlaub H, Stegmaier K, Humphries RK, Serve H, Oellerich T, Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia. Cancer Cell, 31(4):549-562.e11(2017) [pubmed]

10.1016/j.ccell.2017.03.001;

curator keyword: Biomedical

submitter keyword: mass spectrometry, transcriptomics, phosphoproteomics,Acute myeloid leukemia

Henning Urlaub
contact affiliation	Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany Bioanalytics, Georg August University, Robert-Koch-Straße 40, 37073 Göttingen, Germany
contact email	henning.urlaub@mpibpc.mpg.de
lab head
Kuan-Ting Pan
contact affiliation	MPI for Biophysical Chemistry
contact email	kpan@mpibpc.mpg.de
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/2017/06/PXD004192

PRIDE project URI

• PRIDE
  1. PXD004192
     1. Label: PRIDE project
     2. Name: Hoxa9 and Meis1 cooperatively induce addiction to Syk signaling by suppressing miR-146a in acute myeloid leukemia