Barbara J. Graves, PhD
- Signal Transduction
- ETS Family
- DNA-Protein Interactions
- Departments: Oncological Sciences - Professor
- Cancer Center Programs: Nuclear Control of Cell Growth & Differentiation
Academic Office Information
Huntsman Cancer Institute
2000 Circle of Hope, Room: 4380
Salt Lake City, UT 84112
We have set as a long-term goal to understand how a family of highly related DNA binding factors is utilized in biological regulation using the ETS family as a model system. Do individual ETS proteins have unique roles or are there redundancies of function within the family? Specificity would require both a divergence of functionality of individual family members as well as pathways to direct different family members to different gene promoter targets. There is extensive co-expression of ETS family members in a diverse sampling of human cell types. Genome-wide analysis of promoter targets in several of the cell types shows that, in some cases, there is specific matching between specific ETS proteins and specific targets. In other cases, there is co-occupancy by multiple ETS proteins at a specific promoter. We are currently investigating mechanisms of specificity for multiple family members including Ets-1, ETV6, ETV1, ETV4 and ETV5.
|Postdoctoral Fellowship||Carnegie Institution
|Postdoctoral Fellowship||Fred Hutchinson Cancer Research Center
|Doctoral Training||University of Washington
- Autoinhibition of ETV6 DNA Binding Is Established by the Stability of Its Inhibitory Helix.De S, Okon M, Graves BJ, McIntosh LP (2016). Autoinhibition of ETV6 DNA Binding Is Established by the Stability of Its Inhibitory Helix. J Mol Biol, 428(8), 1515-30.
- Conformational Dynamics and the Binding of Specific and Nonspecific DNA by the Autoinhibited Transcription Factor Ets-1.Desjardins G, Okon M, Graves BJ, McIntosh LP (2016). Conformational Dynamics and the Binding of Specific and Nonspecific DNA by the Autoinhibited Transcription Factor Ets-1. Biochemistry, 55(29), 4105-18.
- Synergy of aromatic residues and phosphoserines within the intrinsically disordered DNA-binding inhibitory elements of the Ets-1 transcription factor.Desjardins G, Meeker CA, Bhachech N, Currie SL, Okon M, Graves BJ, McIntosh LP (2014). Synergy of aromatic residues and phosphoserines within the intrinsically disordered DNA-binding inhibitory elements of the Ets-1 transcription factor. Proc Natl Acad Sci U S A, 111(30), 11019-24.
- Autoinhibition of ETV6 (TEL) DNA binding: appended helices sterically block the ETS domain.Coyne HJ 3rd, De S, Okon M, Green SM, Bhachech N, Graves BJ, McIntosh LP (2012). Autoinhibition of ETV6 (TEL) DNA binding: appended helices sterically block the ETS domain. J Mol Biol, 421(1), 67-84.
- Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells.Hollenhorst PC, Ferris MW, Hull MA, Chae H, Kim S, Graves BJ (2011). Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells. Genes Dev, 25(20), 2147-57.
- DNA binding by the ETS protein TEL (ETV6) is regulated by autoinhibition and self-association.Green SM, Coyne HJ 3rd, McIntosh LP, Graves BJ (2010). DNA binding by the ETS protein TEL (ETV6) is regulated by autoinhibition and self-association. J Biol Chem, 285(24), 18496-504.
- Simon L Currie, Desmond K Lau, Jedediah J Doane, Frank G Whitby, Mark Okon, Lawrence P McIntosh, and Barbara J Graves (In Press). Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4, and ETV5. Nucleic Acids Res.