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

Borcherds, Wade and Theillet, François-Xavier and Katzer, Andrea and Finzel, Ana and Mishall, Katie M. and Powell, Anne T. and Wu, Hongwei and Manieri, Wanda and Dieterich, Christoph and Selenko, Philipp and Loewer, Alexander and Daughdrill, Gary W. (2014):
Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells.
In: Nature chemical biology, pp. 1000-2, 10, (12), ISSN 1552-4469,
[Article]

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.

Item Type: Article
Erschienen: 2014
Creators: Borcherds, Wade and Theillet, François-Xavier and Katzer, Andrea and Finzel, Ana and Mishall, Katie M. and Powell, Anne T. and Wu, Hongwei and Manieri, Wanda and Dieterich, Christoph and Selenko, Philipp and Loewer, Alexander and Daughdrill, Gary W.
Title: Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells.
Language: English
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.

Journal or Publication Title: Nature chemical biology
Volume: 10
Number: 12
Divisions: 10 Department of Biology
10 Department of Biology > Systems Biology of the Stress Response
Date Deposited: 02 Sep 2015 08:29
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