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Research Interests
Molecular Chaperones
Research Summary
My laboratory is interested in the roles of molecular chaperones in regulating signal transduction pathways. In particular, we study the function of the cytosolic chaperone Hsp90, which interacts with a diverse subset of client proteins, ranging from steroid hormone receptors to protein kinases. Hsp90, along with a number of co-chaperone proteins, interacts with client proteins in an ordered, ATP-dependent pathway that is conserved from yeast to plants to humans. We use a combined genetic and biochemical approach in Saccharomyces cerevisiae to dissect the individual roles of the co-chaperones in this folding pathway. Current work focuses on characterizing the direct interaction between the Hsp40 Ydj1 and heterologous steroid receptors. Ydj1 binds steroid receptors prior to Hsp90 and the other co-chaperones. In the absence of functional Ydj1, receptor becomes constitutively active, suggesting that Ydj1 interaction is required to bring steroid receptors under hormonal control. Additional studies will focus on understanding the diverse roles of the Hsp90 pathway in the cell cycle. Yeast containing mutations in the Hsp90 pathway exhibit multiple defects in pheromone signaling, such as decreased activity of the Ste11 kinase, which interacts with Hsp90, and decreased processing of both a-factor and alpha factor. By using both heterologous and native client proteins we hope to better understand how the Hsp90 molecular chaperone affects multiple cellular signaling pathways.
Research Publications
2005-2009
Zuehlke A. and J. L. Johnson. Hsp90 and co-chaperones twist the functions of diverse client proteins. Biopolymers. In press. DOI 10.1002/bip.21292
Johnson J. L. and Brown C. Plasticity of the Hsp90 molecular chaperone machine in divergent eukaryotic organisms. Cell Stress and Chaperones. 2009. 14:83-94.
Flom, G.A., M. Lemieszek, E.A. Fortunato, and J.L. Johnson, Farnesylation of Ydj1 is required for in vivo interaction with Hsp90 client proteins. Mol Biol Cell, 2008. 19(12): p. 5249-58
Flom, G., R.H. Behal, L. Rosen, D.G. Cole, and J.L. Johnson, Definition of the minimal fragments of Sti1 required for dimerization, interaction with Hsp70 and Hsp90 and in vivo functions. Biochem J, 2007. 404(1): p. 159-67.
Johnson, J.L., A. Halas, and G. Flom, Nucleotide-dependent interaction of Saccharomyces cerevisiae Hsp90 with the cochaperone proteins Sti1, Cpr6, and Sba1. Mol Cell Biol, 2007. 27(2): p. 768-76.
Flom, G., J. Weekes, J.J. Williams, and J.L. Johnson, Effect of mutation of the tetratricopeptide repeat and asparatate-proline 2 domains of Sti1 on Hsp90 signaling and interaction in Saccharomyces cerevisiae. Genetics, 2006. 172(1): p. 41-51.
Flom, G., J. Weekes, and J.L. Johnson, Novel interaction of the Hsp90 chaperone machine with Ssl2, an essential DNA helicase in Saccharomyces cerevisiae. Curr Genet, 2005. 47(6): p. 368-80.
Aron R, Lopez N, Walter W, Craig EA and Johnson JL. In vivo bipartite interaction between the Hsp40 Sis1 and hsp70 in Saccharomyces cerevisiae. Genetics. 169(4):1873-82. (2005).
Johnson JL and Craig EA (2002) Identifying functional interactions with molecular chaperones. Methods Enzymol 351:442-453.
Hon T, Lee HC, Hach A, Johnson JL, Craig EA, Erdjument-Bromage H, Tempst P, and Zhang L. (2001) The Hsp70-Ydj1 molecular chaperone represses the activity of the heme activator protein Hap1 in the absence of heme. Molec. Cell Biol. 21(23):7923-32.