Cell Biology
Faculty and Research Interests
Dimitri Pestov, PhD
Assistant Professor
Science Center 204A
856-566-6904
pestovdg@umdnj.edu
Education
University of Illinois,
PhD, 1997.
Research Interests
Figure 1. GTP-binding protein Nog1 is detected in the nucleolus of mouse cells by indirect immunofluorescence staining. Nog1 is one of the factors required for the assembly of 60S ribosomal subunits in eukaryotic cells.
One of our research interests is how cells maintain high efficiency and accuracy of ribosome synthesis. Like any other complex assembly process, biosynthesis of ribosomes generates a certain fraction of defective products and kinetically trapped intermediates. How do cells distinguish between ribosomes that are built correctly and those that are not? To learn more about the mechanisms underlying quality control in this system, we are studying the roles of several mammalian nucleolar proteins involved in 60S subunit formation. Using biochemical and molecular approaches, we are also investigating how misassembled preribosomal particles are targeted for degradation.
Figure 2. A variety of adverse metabolic or genetic factors can cause perturbations in ribosome biogenesis. The resulting nucleolar stress activates signaling pathways that may lead to a temporary block of the cell cycle in some cell types, and apoptosis in others.
Another important question that we address in our work is how ribosome biogenesis is interfaced with stress responses and cell cycle control in mammalian cells. In our experiments, we find that errors in ribosome biogenesis occur more often when cells are exposed to various types of metabolic stress. In our previous studies, we have also discovered that perturbations in ribosome assembly have a strong influence on the cell cycle machinery, mediated in part through the tumor suppressor protein p53. By elucidating the mechanisms of cellular surveillance of ribosome synthesis, we hope to better understand the links between biosynthetic processes taking place in the nucleolus and proliferation control in normal and cancer cells.
Selected Publications
- Kent, T., Lapik, Y. R., and Pestov, D. G. (2009). The 5' external transcribed spacer in mouse ribosomal RNA contains two cleavage sites. RNA 15, 14-20.
- Pestov, D. G., Lapik, Y. R., and Lau, L.F. (2008). Assays for ribosomal RNA processing and ribosome assembly. Current Protocols in Cell Biology, 22.11.1-16.
- Lapik, Y. R., Misra, J. M., Lau, L. F., and Pestov, D. G. (2007). Restricting conformational flexibility of the switch II region creates a dominant-inhibitory phenotype in Obg GTPase Nog1. Mol. Cell Biol. 27, 7735-7744.
- Gratenstein, K., Heggestad, A. D., Fortun, J., Notterpek, L., Pestov, D. G., and Fletcher, B. S. (2005) The WD-repeat protein GRWD1: Potential roles in myeloid differentiation and ribosome biogenesis. Genomics 85, 762-773.
- Lapik, Y. R., Fernandes, C. J., Lau, L.F., and Pestov, D. G. (2004). Physical and functional interaction between Pes1 and Bop1 in mammalian ribosome biogenesis. Mol. Cell 15, 17-29.
- Strezoska, Z., Pestov, D. G., and Lau, L. F. (2002). Functional inactivation of the mouse nucleolar protein Bop1 inhibits multiple steps in pre-rRNA processing and blocks cell cycle progression. J. Biol. Chem. 277, 29617-29625.
- Pestov, D. G., Stockelman, M. G., Strezoska, Z., and Lau, L. F. (2001). ERB1, the yeast homolog of mammalian Bop1, is an essential gene required for maturation of the 25S and 5.8S ribosomal RNAs. Nucleic Acids Res. 29, 3621-3630.
- Pestov, D. G., Strezoska, Z., and Lau, L. F. (2001). Evidence of p53-dependent cross-talk between ribosome biogenesis an the cell cycle: effects of nucleolar protein Bop1 on G1/S transition. Mol. Cell Biol. 21, 4246-4255.
- Strezoska, Z., Pestov, D. G., and Lau, L. F. (2000). Bop1 is a mouse WD40 repeat nucleolar protein involved in 28S and 5.8S rRNA processing and 60S ribosome biogenesis. Mol. Cell Biol. 20, 5516-5528.
