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Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.
<div class='caption-title'>BET Proteins Are Molecular Scaffolds Interacting with Distinct Proteins</div>
<div class='caption-title'>Pharmacological BRD Inhibition Modulates the BET Interactome</div>
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
OpenAccess logo Mol Cell 73 621-638.e17 (2019)
Related entries: 5nnc, 5nne, 5nnf, 5nng, 6g0o, 6g0p, 6g0q, 6g0r, 6g0s

Cited: 70 times
EuropePMC logo PMID: 30554943

Abstract

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.

Articles - 5nnd mentioned but not cited (1)

  1. Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. 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. Mol Cell 73 621-638.e17 (2019)


Reviews citing this publication (19)

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Articles citing this publication (50)

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