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Washington University Undergraduate Research Digest: WUURD 4(1)
Peer Editor: Sarah Frazier; Faculty Mentor: Philip D. Stahl
TBC1D3 is a family of oncogenes that has recently appeared in the hominoid lineage. These genes are clustered within a region of chromosome 17 that has experienced extensive intrachromosomal rearrangement and segmental duplication. The TBC1D3 locus is also amplified in select breast and prostate tumors. We have shown that TBC1D3 expression enhances cell proliferation, Epidermal Growth Factor Receptor (EGFR) signaling, and delays EGFR trafficking and degradation in mouse and human cell lines. Here we describe a multi-faceted characterization of TBC1D3, finding binding partners and investigating how it modulates cell signaling. A Yeast-Two-Hybrid screen of TBC1D3 against a human cDNA library yielded a few interesting potential binding partners for TBC1D3, including Cullin7, part of an SCF-like E3 ubiquitin-protein ligase complex, and Nischarin, an anti-apoptotic protein that regulates Rac-1 dependent cell motility. Pull-down experiments of GTP-Ras using the Ras Binding Domain of Raf1 reveal that TBC1D3 also promotes Ras activation in steady- state and growth-factor-stimulated cells. A possible mechanism of interaction with Ras is the adapter protein Grb2, which directly binds to TBC1D3 through its SH2 domain. These studies indicate that TBC1D3 may modulate cell proliferation in hominoids by altering GTP-Ras turnover and interacting with critical signaling molecules.
From the Washington University Undergraduate Research Digest: WUURD, Volume 4, Issue 1, Fall 2008. Published by the Office of Undergraduate Research.
Henry Biggs, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator, Co-editor, and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor.
Srikanth, Priya, "Functional Characterizations of TBC1D3, a Hominoid Oncogene" (2008). Washington University Undergraduate Research Digest, Volume 4, Issue 1.