Loading...
Thumbnail Image
Publication

An order-to-disorder structural switch activates the FoxM1 transcription factor

Marceau, Aimee H.
Brison, Caileen M.
Nerli, Santrupti
Arsenault, Heather E.
McShan, Andrew C.
Chen, Eefei
Lee, Hsiau-Wei
Benanti, Jennifer A
Sgourakis, Nikolaos G.
Rubin, Seth M.
Embargo Expiration Date
Link to Full Text
Abstract

Intrinsically disordered transcription factor transactivation domains (TADs) function through structural plasticity, adopting ordered conformations when bound to transcriptional co-regulators. Many transcription factors contain a negative regulatory domain (NRD) that suppresses recruitment of transcriptional machinery through autoregulation of the TAD. We report the solution structure of an autoinhibited NRD-TAD complex within FoxM1, a critical activator of mitotic gene expression. We observe that while both the FoxM1 NRD and TAD are primarily intrinsically disordered domains, they associate and adopt a structured conformation. We identify how Plk1 and Cdk kinases cooperate to phosphorylate FoxM1, which releases the TAD into a disordered conformation that then associates with the TAZ2 or KIX domains of the transcriptional co-activator CBP. Our results support a mechanism of FoxM1 regulation in which the TAD undergoes switching between disordered and different ordered structures.

Source

Elife. 2019 May 28;8. pii: 46131. doi: 10.7554/eLife.46131. Link to article on publisher's site

Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.7554/eLife.46131
PubMed ID
31134895
Other Identifiers
Notes
Funding and Acknowledgements
Corresponding Author
Related Resources
Related Resources
Repository Citation
Rights
Copyright © 2019, Marceau et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.