PXD015485-1

PXD015485 is an original dataset announced via ProteomeXchange.

Title	Protein-Protein Interactions Maps of the KRAS Pathway in HEK293 and A549 cells
Description	Activating mutations in RAS GTPases drive one fifth of cancers, but poor understandings of many RAS effectors and regulators, and of the roles of their different paralogs, continue to impede drug development. We developed a multi-stage discovery and screening process to understand RAS function and identify RAS-related susceptibilities in lung adenocarcinoma. Using affinity purification mass spectrometry (AP/MS), we generated a protein-protein interaction map of the RAS pathway containing thousands of interactions. From this network we constructed a CRISPR dual knockout library targeting 119 RAS-related genes that we screened for genetic interactions (GIs). We found important new effectors of RAS-driven cellular functions, RADIL and the GEF RIN1, and over 250 synthetic lethal GIs, including a potent KRAS-dependent interaction between RAP1GDS1 and RHOA. Many GIs link specific paralogs within and between gene families. These findings illustrate the power of the multiomic approach to identify synthetic lethal combinations for hitherto undruggable cancers.
HostingRepository	PRIDE
AnnounceDate	2021-07-24
AnnouncementXML	Submission_2021-07-23_17:34:21.634.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD015485
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Janos Demeter
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ammonia-loss; Propionamide; Deamidated; Methyl; Oxidation; Dimethyl; Acetyl
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-17 04:07:00	ID requested
⏵ 1	2021-07-23 17:34:22	announced

Kelly MR, Kostyrko K, Han K, Mooney NA, Jeng EE, Spees K, Dinh PT, Abbott KL, Gwinn DM, Sweet-Cordero EA, Bassik MC, Jackson PK, Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities. Cancer Discov, 10(12):1950-1967(2020) [pubmed]

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

curator keyword: Biomedical

submitter keyword: AP/MS, Protein-protein interaction, KRAS, cancer, GTPase, lung adenocarcinoma

Peter Kent Jackson
contact affiliation	Department of Microbiology & Immunology Stanford University School of Medicine
contact email	pjackson@stanford.edu
lab head
Janos Demeter
contact affiliation	Stanford University
contact email	jdemeter@stanford.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/2021/07/PXD015485

PRIDE project URI

• PRIDE
  1. PXD015485
     1. Label: PRIDE project
     2. Name: Protein-Protein Interactions Maps of the KRAS Pathway in HEK293 and A549 cells