Journal article

Interactome rewiring following pharmacological targeting of BET bromodomains

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.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Lambert, J.-P., Picaud, S. S., Fujisawa, T., Hou, H., Savitsky, P., Uusküla-Reimand, L., Gupta, G., Lin, Z. Y., Tucholska, M., Knight, J. D. R., Gonzalez-Badillo, B., St-Denis, N., Newman, J. A., Stucki, M., Pelletier, L., Bandeira, N., Wilson, M. D., Filippakopoulos, P., & Gingras, A. C. (2018). Interactome rewiring following pharmacological targeting of BET bromodomains. Molecular Cell, 73(3), 621–638.e17 .

MLA Style

Lambert, J-P, et al. “Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.” Molecular Cell, vol. 73, no. 3, 2018, pp. 621–38.e17 .

Chicago Style

Lambert, J-P, SS Picaud, T Fujisawa, et al. 2018. “Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.” Molecular Cell 73 (3): 621–38.e17 .
Print

Access Document

Files:: Lambert et al., Interactome rewiring following pharmacological...

(Preview, Version of record, pdf, 10.3MB, Terms of use)

Publisher copy:: 10.1016/j.molcel.2018.11.006

Authors

+ Lambert, J-P More by this author

Role:: Author

+ Picaud, SS More by this author

Institution:: University of Oxford
Division:: Medical Sciences Division
Department:: NDM
Sub department:: Structural Genomics Consortium
Role:: Author

+ Fujisawa, T More by this author

Role:: Author

+ Hou, H More by this author

Role:: Author

+ Savitsky, P More by this author

Institution:: University of Oxford
Division:: Medical Sciences Division
Department:: NDM
Sub department:: Structural Genomics Consortium
Role:: Author

More authors...

+ Ludwig Institute More from this funder

Funding agency for:: Filippakopoulos, P
Grant:: 095751/Z/11/Z

+ Wellcome Trust More from this funder

Funding agency for:: Filippakopoulos, P
Grant:: 095751/Z/11/Z

Publisher:: Elsevier
Journal:: Molecular Cell More from this journal
Volume:: 73
Issue:: 3
Pages:: 621-638.e17
Publication date:: 2018-12-13
Acceptance date:: 2018-11-02
DOI:: 10.1016/j.molcel.2018.11.006
EISSN:: 1097-4164
ISSN:: 1097-2765

Pubs id:: pubs:941091
UUID:: uuid:235a4867-6778-4fdb-a4e1-a1a69c218d62
Local pid:: pubs:941091
Deposit date:: 2018-11-12
ARK identifier:: ark:/29072/ora_235a486767784fdba4e1a1a69c218d62

Terms of use

Copyright holder:: Lambert et al
Copyright date:: 2018
Notes:: © 2018 The Author(s). Published by Elsevier Inc

Licence:: CC Attribution (CC BY)

Views and Downloads

Views and downloads will return soon

If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP