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Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding

 

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Opened Access Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding
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Author: Díaz Moreno, Irene
Hollingworth, David
Frenkiel, Thomas A.
Kelly, Geoff
Martin, Stephen
Howell, Steven
García Mayoral, María Flor
Gherzi, Roberto
Briata, Paola
Ramos, Andrés
Department: Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular
Date: 2009
Published in: Nature Structural and Molecular Biology, 16 (3), 238-246.
Document type: Article
Abstract: The AU-rich element (ARE)-mediated mRNA-degradation activity of the RNA binding K-homology splicing regulator protein (KSRP) is regulated by phosphorylation of a serine within its N-terminal KH domain (KH1). In the cell, phosphorylation promotes the interaction of KSRP and 14-3-3ζ protein and impairs the ability of KSRP to promote the degradation of its RNA targets. Here we examine the molecular details of this mechanism. We report that phosphorylation leads to the unfolding of the structurally atypical and unstable KH1, creating a site for 14-3-3ζ binding. Using this site, 14-3-3ζ discriminates between phosphorylated and unphosphorylated KH1, driving the nuclear localization of KSRP. 14-3-3ζ –KH1 interaction regulates the mRNA-decay activity of KSRP by sequestering the protein in a separate functional pool. This study demonstrates how an mRNA-degradation pathway is connected to extracellular signaling networks through the reversible unfolding of a protein domain.
Cite: Díaz Moreno, I., Hollingworth, D., Frenkiel, T.A., Kelly, G., Martin, S., Howell, S.,...,Ramos, A. (2009). Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding. Nature Structural and Molecular Biology, 16 (3), 238-246.
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URI: https://hdl.handle.net/11441/84782

DOI: 10.1038/nsmb.1558

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