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Stuart Tsubota Ph.D.
Lennon Hall, Room B23, Tel: 395-5759
My lab works on the genes involved in the control of pyrimidine biosynthesis, their role in the mitotic cell cycle and development, as well as their evolutionary conservation. We use both classical genetics and molecular biological approaches to dissect this phenomenon in Drosophila.
The long-term goal of the laboratory is to elucidate the regulation and function of the enhancer of rudimentary gene, e(r), a gene that may play an important role in human cancers. In eukaryotes, e(r), is expressed at high levels in dividing cells, and is up-regulated in human cancers. This up-regulation increases with tumor progression, leading to the hypothesis that e(r) expression may be diagnostic for cancers and their progression. The data also present the possibility that e(r) may have a causative role in cancer progression. A combination of genetic, biochemical, and expression experiments point to the involvement of e(r) in pyrimidine biosynthesis, DNA synthesis, cell division, transcriptional regulation, and the Notch signaling pathway. Immunolocalization of the e(r) protein, ER, and ER-GFP fusions, localize both the human and Drosophila ER to the nucleus. Consistent with these findings, screens for protein interactors identify a number of nuclear binding partners involved in transcription and DNA replication. ER is a small protein (100-109 amino acids) with a high conservation in primary and secondary structure. The human and Drosophila proteins are both 104 amino acids in length and are 76% identical. This high structural conservation, along with conserved aspects of its expression and cellular localization, suggests that the function of the protein may also be conserved. This is demonstrated by experiments, which show that the human gene can functionally replace the Drosophila gene.
We ultilize a combination of genetic and molecular approaches to study the regulation of the e(r) gene. In particular, we are interested in identifying the genes that are responsible for the activation of e(r) in dividing cells. We are also testing the functional conservation of e(r) by testing the ability of e(r) homologues from a diverse collection of eukaryotes to functionally replace the Drosophila gene.
- Roykhman M, Ibach S, Harding D, Wolff B, Vowels M, Gelsthorpe ME, Wojcik EJ, Rizzo N and Tsubota S. Generation and Analysis of Deficiencies on the X Chromosome Containing the enhancer of rudimentary and CG15352. Fly 1: 4, 245-250 (2007)
- Gelsthorpe ME, Tan Z, Philips A, Eissenberg JC, Miller A, Wallace J and Tsubota S. Regulation of the Drosophila melanogaster Protein, Enhancer of Rudimentary, by Casein Kinase II. Genetics 174: 265-270 (2006)
- Tsubota S, Vogel AC, Phillips AC, Ibach SM, Weber NK, Kostrzebski MA and Spencer SA. Interactions between enhancer of rudimentary and Notch and deltex reveal a regulatory function of enhancer of rudimentary in the Notch signaling pathway in Drosophila melanogaster. Landes Bioscience Fly 5:4, 1-10 (2011)