TY - JOUR TI - An order-to-disorder structural switch activates the FoxM1 transcription factor AU - Marceau, Aimee H AU - Brison, Caileen M AU - Nerli, Santrupti AU - Arsenault, Heather E AU - McShan, Andrew C AU - Chen, Eefei AU - Lee, Hsiau-Wei AU - Benanti, Jennifer A AU - Sgourakis, Nikolaos G AU - Rubin, Seth M A2 - Kay, Lewis E A2 - Wolberger, Cynthia A2 - Kay, Lewis E VL - 8 PY - 2019 DA - 2019/05/28 SP - e46131 C1 - eLife 2019;8:e46131 DO - 10.7554/eLife.46131 UR - https://doi.org/10.7554/eLife.46131 AB - 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. KW - transcription factors KW - intrinsically disordered proteins KW - Cdk KW - Plk1 KW - nuclear magnetic resonance JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -