Faculty and Research Interests
Natalia Shcherbik, PhD
Science Center 206A
State Research Center of Virology and Biotechnology, Russia / Fels Institute for Cancer Research, Temple University School of Medicine, USA, 2003.
Ubiquitination is a process of post-translational protein modification that controls a wide variety of fundamental molecular processes in the eukaryotic cell, such as cell cycle, transcription, antigen presentation, apoptosis, modulation of surface receptors and ion channels, DNA repair, translation and others. The major focus of my work is to understand how ubiquitination controls stability of ribosomes, large ribonucleoprotein complexes that are essential for protein synthesis. In particular, I am interested in uncovering the role for the enzyme ubiquitin-ligase Rsp5p in the process of ribosome degradation. In my studies I use a simple eukaryotic organism, the budding yeast, as a model system.
Another direction of my studies of the mechanisms of ribosomal degradation/ stability is the investigation of RNA degrading enzymes (RNases) that are able to digest ribosomal RNA (rRNA) – the backbone of the ribosome. In particular, our group discovered an unusual ability of the secretory RNase from the T2 family Rny1p to exit the confinement of the Endoplasmic Reticulum (ER) and cleave rRNA in the cytoplasm. Understanding of the molecular mechanism(s) of Rny1p release from the ER may impact our knowledge of the regulation and functioning of other secretory RNases. Some members of the T2 RNase family have been implicated in human diseases, including neurodegeneration and cancer. For example, recently identified mutations in the human RNASET2 gene are associated with the white matter disorders of the human brain.
(Updated September 2015)
- Wang M, Parshin AV, Shcherbik N, Pestov DG. Reduced expression of the mouse ribosomal protein Rpl17 alters the diversity of mature ribosomes by enhancing production of shortened 5.8S rRNA. RNA, 21(7): 1240-8, July 2015.
- Shcherbik N. Golgi-mediated glycosylation determines residency of the T2 RNase Rny1p in Saccharomyces cerevisiae. Traffic, 14(12): 1209-27, December 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.
- Shcherbik N, Pestov DG. Ubiquitin and ubiquitin-like proteins in the nucleolus: multitasking tools for a ribosome factory. Genes Cancer, 1(7): 681-9,Jul 2010.
- 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.
- Bhattacharya S, Shcherbik N, Vasilescu J, Smith JC, Figeys D, Haines DS. Identification of lysines within membrane-anchored Mga2p120 that are targets of Rsp5p ubiquitination and mediate mobilization of tethered Mga2p90. J Mol Biol, 385(3): 718-25, Jan 2009.
- Shcherbik N, Haines DS. Cdc48pNpl4p/Ufd1p binds and segregates heterodimeric membrane anchored/tethered complexes via a polyubiquitin signal present on the anchors. Molecular Cell, 25(3): 385-97, Feb 2007.
- Shcherbik N, Kee Y, Lyon N, Huibregtse JM, Haines DS. A single PXY motif located within the carboxy-terminus of Spt23p and Mga2p mediates a physical and functional interaction with ubiquitin ligase Rsp5p. J Biol Chem, 279(51): 53892-8, Dec 2004.
- Shcherbik N, Haines DS. Ub on the move. J Cell Biochem, 93(1): 11-9, Sep 2004.
- Shcherbik N, Zoladek T, Nickels JT, Haines DS. Rsp5p is required for ER-bound Mga2p120 poly-ubiquitination and release of the processed/tethered transactivator Mga2p90. Curr Biol, 13(14): 1227-1233, Jul 2003.
- Gajewska B, Shcherbik N, Oficjalska D, Haines DS, Zoladek T. Functional analysis of the human orthologue of the RSP5-encoded ubiquitin protein ligase, hNEDD4, in yeast. Curr Genet, 43(1): 1-10, Apr 2003.
- Shcherbik N, Kumar S, Haines DS. Substrate proteolysis is inhibited by dominant-negative Nedd4 and Rsp5 mutants harboring alterations in WW domain 1. J Cell Sci, 115(Pt5): 1041-8, Mar 2002.
- Darbinian N, Gallia GL, Kundu M, Shcherbik N, Tretiakova A, Giordano A, Khalili K. Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1. Oncogene, 18(46): 6398-402, Nov 1999.
- Tretiakova A, Gallia GL, Shcherbik N, Jameson B, Johnson EM, Amini S, Khalili K. Association of Pur alpha with RNAs homologous to 7 SL determines its binding ability to the myelin basic protein promoter DNA sequence. J Biol Chem, 273(35): 22241-7, Aug 1998.
- Safronov IV, Shcherbik NV, Khodyreva SN, Vlasov VA, Dobrikov MI, Shishkin GV, Lavrik OI. New photoreactive N(4)-substituted dCTP analogues: synthesis, photochemical characteristics, and substrate properties in HIV-1 reverse transcriptase catalyzed DNA synthesis. Bioorg Khim, 23(7): 576-85, Jul 1997.
- Shcherbik NV, Khodyreva SN, Vlasov VA, Dobrikov MI, Dymshits GM, Lavrik OI. Photoaffinity modification of human immunodeficiency virus reverse transcriptase with an analog of deoxyuridine-5'-triphosphate, containing an arylazide group. Mol Biol (Mosk), 31(2): 344-52, Mar 1997.