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.

• Klíčová slova
• AlphaPullDown, NF-κB, RELA, breast cancer, interaction, protein complexes, protein correlation profiling, proteomics,
• MeSH
• karcinogeneze metabolismus   MeSH
• lidé MeSH
• mapování interakce mezi proteiny MeSH
• mapy interakcí proteinů * MeSH
• nádorové buněčné linie MeSH
• nádory prsu * metabolismus   patologie   MeSH
• NF-kappa B * metabolismus   MeSH
• proteinarginin-N-methyltransferasy metabolismus   MeSH
• signální transdukce MeSH
• transkripční faktor RelA * metabolismus   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• NF-kappa B * MeSH
• proteinarginin-N-methyltransferasy MeSH
• RELA protein, human MeSH Prohlížeč
• transkripční faktor RelA * MeSH