Lambert JP Picaud S Fujisawa T Hou H Savitsky P Uusküla-Reimand L Gupta GD Abdouni H Lin ZY Tucholska M Knight JDR Gonzalez-Badillo B St-Denis N Newman JA Stucki M Pelletier L Bandeira N Wilson MD Filippakopoulos P Gingras AC 2019 Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1. application/pdf https://sonar.ch/global/documents/260575 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molcel.2018.11.006 info:eu-repo/semantics/altIdentifier/pmid/30554943 info:eu-repo/semantics/openAccess Molecular cell. - 2019 AP-MS BET JQ1 KacY bromodomain nucleolus protein crystallography proteomic network rRNA rewiring Antineoplastic Agents Azepines Cell Cycle Proteins Cell Proliferation Gene Expression Regulation, Neoplastic HEK293 Cells HeLa Cells Humans K562 Cells Models, Molecular Molecular Targeted Therapy Neoplasms Nuclear Proteins Protein Binding Protein Conformation Protein Interaction Domains and Motifs Protein Interaction Maps Protein-Serine-Threonine Kinases Proteomics RNA-Binding Proteins Signal Transduction Structure-Activity Relationship Transcription Factors Triazoles Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. http://purl.org/coar/resource_type/c_6501