Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer.
Mol Cell Proteomics
; 23(4): 100744, 2024 Apr.
Article
de En
| MEDLINE
| ID: mdl-38417630
ABSTRACT
NF-κB pathway is involved in inflammation; however, recent data shows its role also in cancer development and progression, including metastasis. To understand the role of NF-κB interactome dynamics in cancer, we study the complexity of breast cancer interactome in luminal A breast cancer model and its rearrangement associated with NF-κB modulation. Liquid chromatography-mass spectrometry measurement of 160 size-exclusion chromatography fractions identifies 5460 protein groups. Seven thousand five hundred sixty eight interactions among these proteins have been reconstructed by PrInCE algorithm, of which 2564 have been validated in independent datasets. NF-κB modulation leads to rearrangement of protein complexes involved in NF-κB signaling and immune response, cell cycle regulation, and DNA replication. Central NF-κB transcription regulator RELA co-elutes with interactors of NF-κB activator PRMT5, and these complexes are confirmed by AlphaPulldown prediction. A complementary immunoprecipitation experiment recapitulates RELA interactions with other NF-κB factors, associating NF-κB inhibition with lower binding of NF-κB activators to RELA. This study describes a network of pro-tumorigenic protein interactions and their rearrangement upon NF-κB inhibition with potential therapeutic implications in tumors with high NF-κB activity.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du sein
/
Facteur de transcription NF-kappa B
/
Facteur de transcription RelA
/
Cartes d'interactions protéiques
Limites:
Female
/
Humans
Langue:
En
Journal:
Mol Cell Proteomics
/
Mol. cell. proteomics
/
Molecular & cellular proteomics
Sujet du journal:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Année:
2024
Type de document:
Article
Pays d'affiliation:
République tchèque
Pays de publication:
États-Unis d'Amérique