p53 can be viewed as a integrator of stress signals and responses in cells. The widespread attention that p53 has earned stems both from the fact that it is a tumor suppressor gene frequently mutated in many human tumor types, and that it regulates important processes in the cell. DNA tumor virus (SV40, Ad, HPV) modulate p53 function. An important question not yet answered in the p53 field is: what is upstream of p53 and how does it function to signal p53. The overall goals of this application are to elucidate how cells signal to and control the function of p53. Multiple aims deal with evaluating further the role of phosphorylation in regulating p53 function. They include investigating the influence of phosphorylation on p53:Mdm2 interactions, the role of TFIIH associated CAK/p36 kinase in modulating p53 function and the role of phosphorylation events in the c terminus of p53 on p53 function.
Other aims are directed at investigating the significance of the Ref-1:p53 interaction, the role of cyclin G, a p53 responsive gene in modulating p53 effects on cells and the role of p53 in DNA replication/repair.
| Rokudai, Susumu; Li, Yingchun; Otaka, Yukihiro et al. (2018) STXBP4 regulates APC/C-mediated p63 turnover and drives squamous cell carcinogenesis. Proc Natl Acad Sci U S A 115:E4806-E4814 |
| Katz, Chen; Low-Calle, Ana Maria; Choe, Joshua H et al. (2018) Wild-type and cancer-related p53 proteins are preferentially degraded by MDM2 as dimers rather than tetramers. Genes Dev 32:430-447 |
| Lessel, Davor; Wu, Danyi; Trujillo, Carlos et al. (2017) Dysfunction of the MDM2/p53 axis is linked to premature aging. J Clin Invest 127:3598-3608 |
| Karni-Schmidt, Orit; Lokshin, Maria; Prives, Carol (2016) The Roles of MDM2 and MDMX in Cancer. Annu Rev Pathol 11:617-44 |
| Daftuar, Lilyn; Zhu, Yan; Jacq, Xavier et al. (2013) Ribosomal proteins RPL37, RPS15 and RPS20 regulate the Mdm2-p53-MdmX network. PLoS One 8:e68667 |
| Zhu, Yan; Regunath, Kausik; Jacq, Xavier et al. (2013) Cisplatin causes cell death via TAB1 regulation of p53/MDM2/MDMX circuitry. Genes Dev 27:1739-51 |
| Bursa?, Sladana; Brdov?ak, Maja Cokari?; Pfannkuchen, Martin et al. (2012) Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress. Proc Natl Acad Sci U S A 109:20467-72 |
| Biderman, Lynn; Poyurovsky, Masha V; Assia, Yael et al. (2012) MdmX is required for p53 interaction with and full induction of the Mdm2 promoter after cellular stress. Mol Cell Biol 32:1214-25 |
| Poyurovsky, Masha V; Katz, Chen; Laptenko, Oleg et al. (2010) The C terminus of p53 binds the N-terminal domain of MDM2. Nat Struct Mol Biol 17:982-9 |
| Priest, Christina; Prives, Carol; Poyurovsky, Masha V (2010) Deconstructing nucleotide binding activity of the Mdm2 RING domain. Nucleic Acids Res 38:7587-98 |
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