PXD004196-2
PXD004196 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1 |
Description | Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. At the molecular level, the key components of the Notch pathway are the NOTCH-family receptors, the ligands of the DSL (Delta, Serrate, Lag-2) family and the transcription factor CSL [CBF1/RBPJ, Su(H), Lag-1]. Upon ligand binding, the NOTCH Intra-Cellular Domain (NOTCH ICD) translocates into the nucleus and forms a complex with RBPJ to activate the transcription of target genes. In the absence of NOTCH ICD, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 as a novel interactor of RBPJ. We discovered that L3MBTL3 competes with NOTCH ICD for binding to RBPJ. In the absence of NOTCH ICD, RBPJ recruits L3MBTL3 and its co-factor KDM1A [lysine (K)-specific demethylase 1A] to the promoters/enhancers of Notch target genes to promote H3K4me2 demethylation and transcriptional repression. In three distinct cell contexts in which Notch signaling governs cell fate, i.e., mature T-cells as well as brain and breast tumor cells, the loss of L3MBTL3 results in the de-repression of Notch target genes. Finally, the genetic analyses of the homologs of RBPJ and L3MBTL3 in Drosophila melanogaster and Caenorhabditis elegans demonstrate that the functional link between RBPJ/Su(H)/lag-1 and L3MBTL3/dL(3)mbt/lin-61 is evolutionarily conserved, thus identifying L3MBTL3 as a universal modulator of Notch signaling in metazoans. |
HostingRepository | PRIDE |
AnnounceDate | 2017-10-17 |
AnnouncementXML | Submission_2017-10-18_00:07:19.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jean-Francois Rual |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2016-05-23 01:52:20 | ID requested | |
1 | 2017-10-17 01:44:51 | announced | |
⏵ 2 | 2017-10-18 00:07:20 | announced | Updated publication reference for PubMed record(s): 29030483. |
Publication List
Xu T, Park SS, Giaimo BD, Hall D, Ferrante F, Ho DM, Hori K, Anhezini L, Ertl I, Bartkuhn M, Zhang H, Milon E, Ha K, Conlon KP, Kuick R, Govindarajoo B, Zhang Y, Sun Y, Dou Y, Basrur V, Elenitoba-Johnson KS, Nesvizhskii AI, Ceron J, Lee CY, Borggrefe T, Kovall RA, Rual JF, RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1. EMBO J, 36(21):3232-3249(2017) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: Notch, RBPJ, L3MBTL3, KDM1A |
Contact List
Jean-Francois Rual | |
---|---|
contact affiliation | University of Michigan Department of Pathology |
contact email | jrual@med.umich.edu |
lab head | |
Jean-Francois Rual | |
contact affiliation | University of Michigan Department of Pathology |
contact email | jrual@med.umich.edu |
dataset submitter |
Full Dataset Link List
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/2017/10/PXD004196 |
PRIDE project URI |
Repository Record List
[ + ]