Global interactome mapping reveals pro-tumorigenic interactions of NF-κB in breast cancer

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Authors

LAPČÍK Petr STACEY R. Greg POTĚŠIL David KULHÁNEK Petr FOSTER Leonard J. BOUCHAL Pavel

Year of publication 2024
Type Article in Periodical
Magazine / Source Molecular and Cellular Proteomics
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S1535947624000343
Doi http://dx.doi.org/10.1016/j.mcpro.2024.100744
Keywords NF-?B; RELA; Proteomics; Protein complexes; Interaction; Breast cancer; Protein correlation profiling; AlphaPullDown
Attached files
Description NF-?B 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-?B interactome dynamics in cancer, we study the complexity of breast cancer interactome in luminal A breast cancer model and its rearrangement associated with NF-?B modulation. Liquid chromatography-mass spectrometry measurement of 160 size exclusion chromatography (SEC) fractions identifies 5460 protein groups. 7568 interactions among these proteins have been reconstructed by PrInCE algorithm, of which 2564 have been validated in independent datasets. NF-?B modulation leads to rearrangement of protein complexes involved in NF-?B signaling and immune response, cell cycle regulation and DNA replication. Central NF-?B transcription regulator RELA co-elutes with interactors of NF-?B activator PRMT5, and these complexes are confirmed by AlphaPulldown prediction. A complementary immunoprecipitation experiment recapitulates RELA interactions with other NF-?B factors, associating NF-?B inhibition with lower binding of NF-?B activators to RELA. This study describes a network of pro-tumorigenic protein interactions and their rearrangement upon NF-?B inhibition with potential therapeutic implications in tumors with high NF-?B activity.
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