PXD004168-1

PXD004168 is an original dataset announced via ProteomeXchange.

Title	NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence
Description	Senescence, a persistent form of cell cycle arrest, is often associated with a diverse secretome, which provides complex downstream functionality for senescent cells within the tissue microenvironment. We show that oncogene-induced senescence (OIS) is accompanied by a dynamic fluctuation of NOTCH1 activity, which drives a TGF-β-rich secretome, whilst suppressing the senescence-associated pro-inflammatory secretome through inhibition of C/EBPβ. NOTCH1 and NOTCH1-driven TGF-β contribute to ‘lateral induction of senescence’ through a juxtacrine NOTCH-JAG1 pathway. In addition, NOTCH1 inhibition during senescence facilitates upregulation of pro-inflammatory cytokines, promoting lymphocyte recruitment and senescence surveillance in vivo. Because enforced activation of NOTCH1 signalling confers a near mutually exclusive secretory profile compared to typical senescence, our data collectively indicate that the dynamic alteration of NOTCH1 activity during senescence dictates a functional balance between these two distinct secretomes: one representing TGF-β and the other pro-inflammatory cytokines, highlighting that NOTCH1 is a temporospatial controller of secretome composition.
HostingRepository	PRIDE
AnnounceDate	2016-08-03
AnnouncementXML	Submission_2016-08-03_04:43:45.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yagnesh Umrania
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2016-05-17 08:59:37	ID requested
⏵ 1	2016-08-03 04:43:46	announced
2	2024-10-22 04:29:23	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: Senescence, NOTCH, RAS, plasma membrane profiling, SILAC

Masashi Narita
contact affiliation	University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.
contact email	masashi.narita@cruk.cam.ac.uk
lab head
Yagnesh Umrania
contact affiliation	University of Cambridge
contact email	yu206@cam.ac.uk
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/2016/08/PXD004168

PRIDE project URI

• PRIDE
  1. PXD004168
     1. Label: PRIDE project
     2. Name: NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence