PXD022255

PXD022255 is an original dataset announced via ProteomeXchange.

Title	TMT-MS2_cellular adaptation to hypomorphic alleles of essential gene NUP58
Description	Adaptive evolution in response to cellular stress is a critical process implicated in a wide range of core biological and clinical phenomena. Two major routes of adaptation have been identified: non-genetic cellular plasticity, which allows expression of different phenotypes in novel environments, and genetic variation achieved by selection of fitter phenotypes. While these processes are now broadly accepted, their temporal and epistatic features in the context of cellular evolution and emerging drug resistance are contentious. In this project, we generated hypomorphic alleles of the essential nuclear pore complex (NPC) gene NUP58. By dissecting both early and long-term mechanisms of adaptation in independent clones, we observed that early physiological adaptation correlated with transcriptome rewiring and upregulation of genes known to interact with the NPC. In contrast, long-term adaptation and fitness recovery occurred via focal amplification of NUP58 and restoration of mutant protein expression. These data support the concept that plasticity-mediated and genetic routes can co-exist to enable cellular evolution, with early flexibility of phenotype allowing later acquisition of genetic adaptations to a specific impairment. We propose this approach as a genetic model to mimic targeted drug therapy in human cells and to dissect early and late mechanisms of adaptation. Targeting both mechanisms in parallel may reduce the emergence of drug resistance.
HostingRepository	PRIDE
AnnounceDate	2021-11-02
AnnouncementXML	Submission_2021-11-02_05:11:32.077.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-30 02:26:24	ID requested
⏵ 1	2021-11-02 05:11:33	announced

Targa A, Larrimore KE, Wong CK, Chong YL, Fung R, Lee J, Choi H, Rancati G, Non-genetic and genetic rewiring underlie adaptation to hypomorphic alleles of an essential gene. EMBO J, 40(21):e107839(2021) [pubmed]

submitter keyword: NUP58, essential gene, CRISPR-Cas9, TMT-MS2, cellular adaptation

Giulia Rancati
contact affiliation	A*STAR-SRIS
contact email	altea.targa@sris.a-star.edu.sg
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.de
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/2021/11/PXD022255

PRIDE project URI

• PRIDE
  1. PXD022255
     1. Label: PRIDE project
     2. Name: TMT-MS2_cellular adaptation to hypomorphic alleles of essential gene NUP58