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This article is part of the supplement: International Workshop on Computational Systems Biology: Approaches to Analysis of Genome Complexity and Regulatory Gene Networks

Open Access Research

Differences in the transactivation domains of p53 family members: a computational study

Jagadeesh N Mavinahalli12, Arumugam Madhumalar1, Roger W Beuerman2, David P Lane3 and Chandra Verma1*

Author affiliations

1 Bioinformatics Institute (A-STAR), 30 Biopolis Street, Matrix, Singapore 138671

2 Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751

3 Institute of Molecular and Cell Biology (A-STAR), 61 Biopolis Drive, Proteos, Singapore 138673

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Citation and License

BMC Genomics 2010, 11(Suppl 1):S5  doi:10.1186/1471-2164-11-S1-S5

Published: 10 February 2010

Abstract

The N terminal transactivation domain of p53 is regulated by ligases and coactivator proteins. The functional conformation of this region appears to be an alpha helix which is necessary for its appropriate interactions with several proteins including MDM2 and p300. Folding simulation studies have been carried out to examine the propensity and stability of this region and are used to understand the differences between the family members with the ease of helix formation following the order p53 > p73 > p63. It is clear that hydrophobic clusters control the kinetics of helix formation, while electrostatic interactions control the thermodynamic stability of the helix. Differences in these interactions between the family members may partially account for the differential binding to, and regulation by, MDM2 (and MDMX). Phosphorylations of the peptides further modulate the stability of the helix and control associations with partner proteins.