PXD027619-1

PXD027619 is an original dataset announced via ProteomeXchange.

Title	Modulation of the NOTCH1 pathway by LUNATIC FRINGE is dominant over that of MANIC or RADICAL FRINGE
Description	Fringes are glycosyltransferases that transfer a GlcNAc to O-fucose residues on Epidermal Growth Factor-like (EGF) repeats. Three Fringes exist in mammals: LUNATIC FRINGE (LFNG), MANIC FRINGE (MFNG) and RADICAL FRINGE (RFNG). Fringe modification of O-fucose on EGF repeats in the NOTCH1 (N1) extracellular domain modulates the activation of N1 signaling. Not all O-fucose residues of N1 are modified by all Fringes; some are modified by one or two Fringes and others not modified at all. The distinct effects on N1 activity depend on which Fringe is expressed in a cell. However, little data is available on the effect that more than one Fringe has on the modification of O-fucose residues and the resulting downstream consequence on Notch activation. Using mass spectral glycoproteomic site mapping and cell-based N1 signaling assays, we compared the effect of co-expression of N1 with one or more Fringes on modification of O-fucose and activation of N1 in three cell lines. Individual expression of each Fringe with N1 in the three cell lines revealed differences in modulation of the Notch pathway dependent on the presence of endogenous Fringes. Despite these cell-based differences, co-expression of several Fringes with N1 demonstrated a dominant effect of LFNG over MFNG or RFNG. MFNG and RFNG appeared to be co-dominant but strongly dependent on the ligands used to activate N1 and on the endogenous expression of Fringes. These results show a hierarchy of Fringe activity and indicate that the effect of MFNG and/or RFNG could be small in the presence of LFNG.
HostingRepository	PRIDE
AnnounceDate	2021-09-28
AnnouncementXML	Submission_2021-09-28_13:57:47.097.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	FLORIAN PENNARUBIA
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-28 02:30:45	ID requested
⏵ 1	2021-09-28 13:57:47	announced

Dataset with its publication pending

submitter keyword: NOTCH1, Fringe, EGF-like domains, O-fucosylation, glycosylation

Robert S Haltiwanger
contact affiliation	Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
contact email	rhalti@uga.edu
lab head
FLORIAN PENNARUBIA
contact affiliation	Complex Carbohydrate Research Center (CCRC), University of Georgia
contact email	florian.pennarubia@uga.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027619
     1. Label: PRIDE project
     2. Name: Modulation of the NOTCH1 pathway by LUNATIC FRINGE is dominant over that of MANIC or RADICAL FRINGE