Faculty and Research Interests
Dimitri Pestov, PhD
Science Center 204A
University of Illinois,
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.
(Updated March 2013)
- Pestov DG, Shcherbik N. Rapid cytoplasmic turnover of yeast ribosomes in response to rapamycin inhibition of TOR. Mol Cell Biol, 32(11): 2135-44, Jun 2012.
- Shcherbik N, Pestov DG. The ubiquitin ligase Rsp5 is required for ribosome stability in Saccharomyces cerevisiae. RNA, 17(8): 1422-8, Aug 2011.
2. Wang M, Pestov DG. 5'-end surveillance by Xrn2 acts as a shared mechanism for mammalian pre-rRNA maturation and decay. Nucleic Acids Res, 39(5): 1811-22, Mar 2011.
3. Shcherbik N, Pestov DG. Ubiquitin and ubiquitin-like proteins in the nucleolus: multitasking tools for a ribosome factory. Genes Cancer, 1(7): 681-689, July 2010.
4. Srivastava L, Lapik YR, Wang M, Pestov DG. Mammalian DEAD box protein Ddx51 acts in 3' end maturation of 28S rRNA by promoting the release of U8 snoRNA. Mol Cell Biol, 30(12): 2947-56, Jun 2010.
5. Shcherbik N, Wang M, Lapik YR, Srivastava L, Pestov DG. Polyadenylation and degradation of incomplete RNA polymerase I transcripts in mammalian cells. EMBO Rep, 11(2): 106-11, Feb 2010.
6. Kent T, Lapik YR, Pestov DG. The 5' external transcribed spacer in mouse ribosomal RNA contains two cleavage sites. RNA, 15(1): 14-20, Jan 2009.
7. Pestov DG, Lapik YR, Lau LF. Assays for ribosomal RNA processing and ribosome assembly. Curr Protoc Cell Biol, Chapter 22: Unit 22.11, Jun 2008.
8. Lapik YR, Misra JM, Lau LF, Pestov DG. Restricting conformational flexibility of the switch II region creates a dominant-inhibitory phenotype in Obg GTPase Nog1. Mol Cell Biol, 27(21): 7735-44, Nov 2007.
9. Lapik YR, Fernandes CJ, Lau LF, Pestov DG. Physical and functional interaction between Pes1 and Bop1 in mammalian ribosome biogenesis. Mol Cell, 15(1): 17-29, Jul 2004.
10. Pestov DG, Strezoska Z, Lau LF. Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: effects of nucleolar protein Bop1 on G(1)/S transition. Mol Cell Biol, 21(13): 4246-55, Jul 2001.