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Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells

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Official URL:https://doi.org/10.1038/nchembio.1668
PubMed:View item in PubMed
Creators Name:Borcherds, W. and Theillet, F.X. and Katzer, A. and Finzel, A. and Mishall, K.M. and Powell, A.T. and Wu, H. and Manieri, W. and Dieterich, C. and Selenko, P. and Loewer, A. and Daughdrill, G.W.
Journal Title:Nature Chemical Biology
Journal Abbreviation:Nat Chem Biol
Page Range:1000-1002
Date:December 2014
Keywords:Cell Cycle, Tumor Cell Line, DNA Damage, Escherichia coli, Gamma Rays, Gene Expression Regulation, Intrinsically Disordered Proteins, Molecular Models, Mutation, Protein Folding, Proto-Oncogene Proteins c-mdm2, Recombinant Proteins, Secondary Protein Structure, Signal Transduction, Tertiary Protein Structure, Tumor Suppressor Protein p53
Abstract:Levels of residual structure in disordered interaction domains determine in vitro binding affinities, but whether they exert similar roles in cells is not known. Here, we show that increasing residual p53 helicity results in stronger Mdm2 binding, altered p53 dynamics, impaired target gene expression and failure to induce cell cycle arrest upon DNA damage. These results establish that residual structure is an important determinant of signaling fidelity in cells.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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