PXD004196

PXD004196 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biological

submitter keyword: Notch, RBPJ, L3MBTL3, KDM1A

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

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PRIDE project URI

• PRIDE
  1. PXD004196
     1. Label: PRIDE project
     2. Name: RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1