A protein interaction landscape of breast cancer.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
21
10
2021
Statut:
ppublish
Résumé
Cancers have been associated with a diverse array of genomic alterations. To help mechanistically understand such alterations in breast-invasive carcinoma, we applied affinity purification–mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer (BC) proteins, with and without relevant mutations, across three human breast cell lines. These networks identify cancer-specific protein-protein interactions (PPIs), interconnected and enriched for common and rare cancer mutations, that are substantially rewired by the introduction of key BC mutations. Our analysis identified BPIFA1 and SCGB2A1 as PIK3CA-interacting proteins, which repress PI3K-AKT signaling, and uncovered USP28 and UBE2N as functionally relevant interactors of BRCA1. We also show that the protein phosphatase 1 regulatory subunit spinophilin interacts with and regulates dephosphorylation of BRCA1 to promote DNA double-strand break repair. Thus, PPI landscapes provide a powerful framework for mechanistically interpreting disease genomic data and can identify valuable therapeutic targets.
Identifiants
pubmed: 34591612
doi: 10.1126/science.abf3066
pmc: PMC9040556
mid: NIHMS1796644
doi:
Substances chimiques
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabf3066Subventions
Organisme : NCI NIH HHS
ID : R50 CA243885
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103504
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA138804
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA262227
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA239333
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209891
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA239336
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA184427
Pays : United States
Commentaires et corrections
Type : CommentIn
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