Wild-type p53 transmits signals from genotoxic stress to genes and factors that regulate cell growth and cell death. p53 mutation is a highly frequent event inmany of the major forms of human cancer. In at least half of these tumors, mutant forms of p53 protein are expresssed, frequently at high levels. Despite the advanced level of understanding of the structure and functions of the normal, wild-type form of p53 protein, there is still much to learn about the properties of tumor- derived mutant forms of p53. The goals of the proposed research are to study the """"""""hot spot"""""""" mutant proteins in terms of their structural charactertistics, modifications and DNA binding properties. It is planned to examine and screen for ways to convert mutant p53 proteins to ones that are more wild-type in conformation. The attributes of mutant forms of p53 which confer prooncogenic properties upon cells will be examined. Finally, it is also intended to assess the impact of p53 status on the response of tumor cells to antineoplastic agents.
| Laptenko, Oleg; Shiff, Idit; Freed-Pastor, Will et al. (2015) The p53 C terminus controls site-specific DNA binding and promotes structural changes within the central DNA binding domain. Mol Cell 57:1034-1046 |
| Rokudai, Susumu; Laptenko, Oleg; Arnal, Suzzette M et al. (2013) MOZ increases p53 acetylation and premature senescence through its complex formation with PML. Proc Natl Acad Sci U S A 110:3895-900 |
| Laptenko, Oleg; Prives, Carol (2013) Anything but simple: a phosphorylation-driven toggle within Brd4 triggers gene-specific transcriptional activation. Mol Cell 49:838-9 |
| Laptenko, Oleg; Prives, Carol (2012) The p53-HAT connection: PCAF rules? Cell Cycle 11:2975-6 |
| Barsotti, Anthony M; Beckerman, Rachel; Laptenko, Oleg et al. (2012) p53-Dependent induction of PVT1 and miR-1204. J Biol Chem 287:2509-19 |
| Freed-Pastor, William A; Mizuno, Hideaki; Zhao, Xi et al. (2012) Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell 148:244-58 |
| Freed-Pastor, William A; Prives, Carol (2012) Mutant p53: one name, many proteins. Genes Dev 26:1268-86 |
| Singer, Stephan; Zhao, Ruiying; Barsotti, Anthony M et al. (2012) Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes. Mol Cell 48:799-810 |
| Laptenko, Oleg; Beckerman, Rachel; Freulich, Ella et al. (2011) p53 binding to nucleosomes within the p21 promoter in vivo leads to nucleosome loss and transcriptional activation. Proc Natl Acad Sci U S A 108:10385-90 |
| Beckerman, Rachel; Prives, Carol (2010) Transcriptional regulation by p53. Cold Spring Harb Perspect Biol 2:a000935 |
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