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-Structure paper
タイトル | Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. |
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ジャーナル・号・ページ | Mol Cell, Vol. 73, Issue 3, Page 621-638.e17, Year 2019 |
掲載日 | 2019年2月7日 |
著者 | Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R Knight / Beatriz Gonzalez-Badillo / Nicole St-Denis / Joseph A Newman / Manuel Stucki / Laurence Pelletier / Nuno Bandeira / Michael D Wilson / Panagis Filippakopoulos / Anne-Claude Gingras / |
PubMed 要旨 | 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, ...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. |
リンク | Mol Cell / PubMed:30554943 / PubMed Central |
手法 | SAS (X-ray synchrotron) / X線回折 |
解像度 | 1.15 - 2.22 Å |
構造データ | SASDCR2: SASDCS2: SASDCT2: SASDCU2: PDB-5nnc: PDB-5nnd: PDB-5nne: PDB-5nnf: PDB-5nng: PDB-6g0o: PDB-6g0p: PDB-6g0q: PDB-6g0r: PDB-6g0s: |
化合物 | ChemComp-HOH: ChemComp-EDO: |
由来 |
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キーワード | TRANSCRIPTION / Bromodomain / complex / Structural Genomics / Structural Genomics Consortium / SGC |