U of M: Department of Genetics, Cell Biology and Development

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Deanna Koepp, Ph.D.

Assistant Professor

Immediate opening to study the role of the S. cerevisiae F-box protein Dia2
and it interaction partners in DNA replication and the maintenance of genomic stability.
Applicants must have a Ph.D. and a strong background in molecular biology. Experience with genetic model organisms is preferred. International applicants should have at least 2 publications in English language journals. To apply, please send a cv and three letters of reference to koepp015@umn.edu.

Areas of Research: Research Techniques: Research Interests: Selected Publications

Postdoctoral position available

Mailing Address: University of Minnesota Department of Genetics, Cell Biology, and Development 6-160 Jackson 321 Church St. SE Minneapolis, MN 55455 USA		Education: Ph. D. Harvard University, 1998
Office: 4-126 MCB P: 612-624-4201 F: 612-625-4648 Email: koepp015@umn.edu	Lab: 4-182 MCB P: 612-624-4807

Areas of Research Strength:

Cell cycle regulation
Ubiquitination and proteolysis
Genetic mechanisms of tumorigenesis
Nucleocytoplasmic trafficking

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Research Techniques:

Molecular genetics and cell biology
Fluorescent microscopy
Ubiquitin biochemistry

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Research Interests:

Cell growth and division is coordinately regulated to follow a scripted program
of events. Perturbation of the cell cycle can lead to genomic instability
or tumorigenesis. Cell cycle progression is controlled by factors whose expression
oscillates throughout the cell cycle. One key mechanism for regulating the expression
of cell cycle factors is ubiquitin-dependent proteolysis.

The Koepp laboratory investigates the role of a family of modular
ubiquitin ligases, enzymes that regulate the ubiquitination of target proteins,
in cell cycle regulation. These ubiquitin ligases, called SCF complexes, are
composed of at least four subunits: Skp1, Cdc53/Cullin, Rbx1/Roc1 and an
F-box-containing protein. Skp1, Cdc53/Cullin and Rbx1/Roc1 are core
components of each SCF complex, while the F-box protein determines
substrate specificity. A large family of F box proteins has been identified,
suggesting thatSCF complexes regulate the ubiquitination of numerous
substrates. SCF complexes are conserved among eukaryotes; thus
both human cells and the yeast Saccharomyces cerevisiae are used
as systems to study SCF function. The power of yeast genetics is used
in S. cerevisiae while human cells are used for cell biology and
biochemistry studies.

Downregulation of protein function via proteolysis-dependent mechanisms
is important for many cellular functions. SCF complexes are likely to be used
in many pathways, given their combinatorial nature and the extraordinary numbers
of F-box proteins in higher eukaryotes. The development of a generalized mechanism
for SCF complexes will have tremendous utility to many fields of molecular research.
Thus, it is important to understand how the SCF functions and how it is regulated,
particularly in mammalian cells. Furthermore, determining how and why proteins
are targeted for destruction could have enormous implications in drug design. The
lab has discovered an SCF complex that ubiquitinates the cell cycle factor cyclin E
and is studying the mechanism and regulation of the association of cyclin E with this
complex not only as a model for SCF function but also to understand the implications f
or cell cycle control.

There are many F-box proteins for which no substrate has been identified. Also,
putative substrates of SCF complexes have been identified but the identity of their
cognate F-box protein is unknown. Even in the case of known SCF substrates, such
as cyclin E, additional SCF complexes may play a role in their regulation. To address
these issues, the lab is developing systematic assays to identify substrate/F-box
protein interactions.

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Selected Publications:

Swaminathan, S., Kile, A.C., MacDonald, E.M., Koepp, D.M. Yra1 is required for S phase entry and affects Dia2 binding to replication origins, Mol. Cell. Biol., 2007 Jul; 27(13):4674-84. Epub 2007 Apr 23.

Kang, Y., Zhang, N., Koepp, D.M., Walters, K.J. Ubiquitin receptor proteins hHR23a and hPLIC2 interact. J. Mol. Biol., 2007 Jan 26; 365(4):1093-101.

Zhang, W. and Koepp, D.M. Fbw7 isoform interaction contributes to cyclin E proteolysis. Mol. Cancer Res., 2006 Dec, 4(12):935-43.

F. Liu, N. Zhang, X. Zhou, P.E. Hanna, C.R. Wagner, D.M. Koepp, K.J. Walters, Arylamine Nacetyltransferase aggregation and constitutive ubiquitylation, J. Mol. Biol. (2006) Aug 18;361(3):482-92.

D.M. Koepp, A.C. Kile#, S. Swaminathan#, V. Rodriguez-Rivera, The F-box protein Dia2 regulates DNA Replication, Mol. Biol. Cell, 2006 Apr, 17(4):1540-8, Epub Jan 18. #indicates equal contribution

Koepp, D.M., Schaefer, L.K., Ye, X., Keyomarsi, K., Chu, C., Harper, J.W., Elledge, S.J. (2001) Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science, 294:173-177, published online 30 August (10.1126/science.1065203).

Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W. (1999) A family of mammalian F-box proteins. Curr. Biol. 9:1180-2.

Koepp, D.M., Harper, J.W., Elledge. S.J. (1999) How the Cyclin Became a Cyclin: Regulated Proteolysis in the Cell Cycle. Cell. 97:431-434.

Kamura T., Koepp D.M., Conrad M.N., Skowyra D., Moreland R.J., Iliopoulos O., Lane W.S., Kaelin W.G. Jr,Elledge S.J., Conaway R.C., Harper J.W., Conaway J.W. (1999) Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science 284:657-61.

Skowyra D., Koepp D.M., Kamura T., Conrad M.N., Conaway R.C., Conaway J.W., Elledge S.J., Harper J.W. (1999) Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science 284:662-5.

To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
search menu should say PubMed
type Koepp DM in the avaliable line

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