PXD039008-2

PXD039008 is an original dataset announced via ProteomeXchange.

Title	A Spatiotemporal Notch Interaction Map from Membrane to Nucleus
Description	Notch signaling relies on ligand-induced proteolysis to liberate a nuclear effector that drives cell fate decisions. The location and timing of individual steps required for proteolysis and movement of Notch from membrane to nucleus, however, remain unclear. Here, we use proximity labeling with quantitative multiplexed mass spectrometry to monitor the microenvironment of endogenous Notch2 after ligand stimulation in the presence of a gamma secretase inhibitor and then as a function of time after inhibitor removal. Our studies show that gamma secretase cleavage of Notch2 occurs in an intracellular compartment and that formation of nuclear complexes and recruitment of chromatin-modifying enzymes occurs within 45 minutes of inhibitor washout. This work provides a spatiotemporal map of unprecedented detail tracking the itinerary of Notch from membrane to nucleus after activation and identifies molecular events in signal transmission that are potential targets for modulating Notch signaling activity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:51:48.985.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marian Kalocsay
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-20 23:31:02	ID requested
1	2023-07-03 10:11:33	announced
⏵ 2	2024-10-22 05:51:49	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: NOTCH signaling, TMT, Gamma Secretase, NOTCH2, Proximity Proteomics

Steve Blacklow
contact affiliation	Chair, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
contact email	Stephen_Blacklow@hms.harvard.edu
lab head
Marian Kalocsay
contact affiliation	The University of Texas MD Anderson Cancer Center
contact email	marian_kalocsay@hms.harvard.edu
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/2023/07/PXD039008

PRIDE project URI

• PRIDE
  1. PXD039008
     1. Label: PRIDE project
     2. Name: A Spatiotemporal Notch Interaction Map from Membrane to Nucleus