Dataset Information


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

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.


PROVIDER: S-EPMC6538375 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2008-01-01 | S-EPMC2311362 | BioStudies
2016-01-01 | S-EPMC4822595 | BioStudies
2012-01-01 | S-EPMC3534135 | BioStudies
2007-01-01 | S-EPMC1855428 | BioStudies
2016-01-01 | S-EPMC4712144 | BioStudies
2012-01-01 | S-EPMC3290704 | BioStudies
2009-01-01 | S-EPMC2765525 | BioStudies
1000-01-01 | S-EPMC2670858 | BioStudies
1000-01-01 | S-EPMC2672497 | BioStudies
2011-01-01 | S-EPMC3083713 | BioStudies