PXD055643

PXD055643 is an original dataset announced via ProteomeXchange.

Title	Paralog protein compensation preserves protein-protein interaction networks following gene loss cancer
Description	Abstract Proteins operate within dense interconnected networks, where interactions are necessary both for stabilising proteins and enabling them to execute their molecular functions. Remarkably, the protein-protein interaction networks operating within tumour cells continue to function despite widespread genetic perturbations. Previous work has demonstrated that tumour cells tolerate perturbations of paralogs better than perturbations of singleton genes but the mechanistic means by which paralogs tolerate perturbation remain poorly characterised. Here we systematically profile the proteomic response of tumours and tumour cell lines to gene loss. We find many examples of both active compensation, where deletion of one paralog results in increased abundance of another, and collateral loss, where deletion of one paralog results in reduced abundance of another. Active compensation is enriched among sequence-similar paralog pairs that have high protein-protein interaction degree and that are widely conserved across evolution. Active compensation is also significantly more likely to be observed for gene pairs with a known synthetic lethal relationship. Compensating paralogs have more ubiquitination sites, suggesting a role for post-transcriptional control by protein degradation. Our results support a model whereby loss of one gene results in increased protein abundance of its paralog, stabilising the protein-protein interaction network. Consequently, tumour cells become dependent on the paralog for survival, creating potentially targetable vulnerabilities.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_00:40:36.493.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD055643
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kieran Wynne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-06 13:25:55	ID requested
⏵ 1	2025-05-07 00:40:36	announced

10.6019/PXD055643;

submitter keyword: protein-protein interaction, compensation,Paralog protein, cancer.

Dr Colm Ryan
contact affiliation	Associate Professor Bioinformatics, UCD School of Medicine, Conway Institute, Systems Biology Ireland, University College Dublin.
contact email	colm.ryan@ucd.ie
lab head
Kieran Wynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055643
     1. Label: PRIDE project
     2. Name: Paralog protein compensation preserves protein-protein interaction networks following gene loss cancer