DSpace Repository

Activation of p53 function by human transcriptional coactivator PC4: Role of protein-protein interaction, DNA bending, and Posttranslational modifications

Show simple item record

dc.contributor.author Batta, Kiran
dc.contributor.author Kundu, Tapas K
dc.date.accessioned 2012-01-24T06:44:14Z
dc.date.available 2012-01-24T06:44:14Z
dc.date.issued 2007-11
dc.identifier 0270-7306 en_US
dc.identifier.citation Molecular and Cellular Biology 27(21), 7603-7614 (2007) en_US
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/243
dc.description Restricted Access en_US
dc.description.abstract Tumor suppressor p53 controls cell cycle checkpoints and apoptosis via the transactivation of several genes that are involved in these processes. The functions of p53 are regulated by a wide variety of proteins, which interact with it either directly or indirectly. The multifunctional human transcriptional coactivator PC4 interacts with p53 in vivo and in vitro and regulates its function. Here we report the molecular mechanisms of the PC4-mediated activation of p53 function. PC4 interacts with the DNA binding and C-terminal domains of p53 through its DNA binding domain, which is essential for the stimulation of p53 DNA binding. Remarkably, ligation-mediated circularization assays reveal that PC4 induces significant bending in the DNA double helix. Deletion mutants defective in DNA bending are found to be impaired in activating p53-mediated DNA binding and apoptosis. Furthermore, acetylation of PC4 enhances, while phosphorylation abolishes, its ability to bend DNA, activate p53 DNA binding, and, thereby, regulate p53 functions. In conclusion, PC4 activates p53 recruitment to p53-responsive promoters (Bar and p21) in vivo through its interaction with p53 and by providing bent substrate for p53 recruitment. These results elucidate the general molecular mechanisms of activation of p53 function, mediated by its coactivators. en_US
dc.description.uri http://dx.doi.org/10.1128/MCB.01064-07 en_US
dc.language.iso en en_US
dc.publisher American Society for Microbiology en_US
dc.rights © 2007 American Society for Microbiology en_US
dc.subject Binding en_US
dc.subject Acetylation en_US
dc.subject MDM2 en_US
dc.subject Phosphorylation en_US
dc.subject Domain en_US
dc.subject Pathway en_US
dc.subject Acetyltransferase en_US
dc.subject Degradation en_US
dc.subject Methylation en_US
dc.title Activation of p53 function by human transcriptional coactivator PC4: Role of protein-protein interaction, DNA bending, and Posttranslational modifications en_US
dc.type Article en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account