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

Autor:	Marceau AH; Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States., Brison CM; Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States., Nerli S; Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States.; Department of Computer Science, University of California, Santa Cruz, Santa Cruz, United States., Arsenault HE; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States., McShan AC; Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States., Chen E; Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States., Lee HW; Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States., Benanti JA; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States., Sgourakis NG; Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States., Rubin SM; Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2019 May 28; Vol. 8. Date of Electronic Publication: 2019 May 28.
DOI:	10.7554/eLife.46131
Abstrakt:	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. Competing Interests: AM, CB, SN, HA, AM, EC, HL, JB, NS, SR No competing interests declared (© 2019, Marceau et al.)
Databáze:	MEDLINE
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