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dc.contributor.authorBatta, Kiran-
dc.contributor.authorKundu, Tapas K-
dc.date.accessioned2012-01-24T06:44:14Z-
dc.date.available2012-01-24T06:44:14Z-
dc.date.issued2007-11-
dc.identifier0270-7306en_US
dc.identifier.citationMolecular and Cellular Biology 27(21), 7603-7614 (2007)en_US
dc.identifier.urihttps://libjncir.jncasr.ac.in/xmlui/10572/243-
dc.descriptionRestricted Accessen_US
dc.description.abstractTumor 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.urihttp://dx.doi.org/10.1128/MCB.01064-07en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.rights© 2007 American Society for Microbiologyen_US
dc.subjectBindingen_US
dc.subjectAcetylationen_US
dc.subjectMDM2en_US
dc.subjectPhosphorylationen_US
dc.subjectDomainen_US
dc.subjectPathwayen_US
dc.subjectAcetyltransferaseen_US
dc.subjectDegradationen_US
dc.subjectMethylationen_US
dc.titleActivation of p53 function by human transcriptional coactivator PC4: Role of protein-protein interaction, DNA bending, and Posttranslational modificationsen_US
dc.typeArticleen_US
Appears in Collections:Research Papers (Tapas K. Kundu)

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