Faithful transmission of the genome to progeny cells is a fundamental process required by all organisms. Errors in this process cause several common human diseases like Downs syndrome and cancer. The machinery that controls the eukaryotic cell cycle is very evolutionarily conserved. We study the control of the cell cycle by protein phosphatase-1 in the single-celled, eukaryote Saccharomyces cerevisiae, or budding yeast. Although this organism has been used for millennia for baking and brewing, we exploit its powerful molecular genetic tools to unravel how the machinery of cell division is regulated. The Glc7, protein phosphatase-1 associates with several noncatalytic regulatory subunits. The holoenzyme formed with Sds22 resides in the nucleus and is responsible for dephosphorylating proteins required for the metaphase to anaphase transition. Our genetic analysis revealed that Glc8 activates and Frp3 inhibits the activity of Glc7. Both Glc8 and Fpr3 modulate Glc7 activity by affecting Glc7 conformation like chaperones. Indeed, Fpr3 is a protein proline isomerase. Glc8 only functions when it is phosphorylated. We found that Glc8 is phosphorylated by cyclin-dependent protein kinase, Pho85. Glc8 kinase primarily stems from two of the ten Pho85 cyclins, Pcl6 and Pcl7. These cyclins appear to maximize their levels in S-phase. Therefore, the pathway that activates Glc7 by Glc8 is throttled on in S-phase, just prior to the requirement for Glc7 in metaphase. We are currently exploring the inputs to the Pcl6 and Pcl7 regulation to understand how the cell exploits this regulatory network. All these yeast proteins are conserved in humans. Therefore, we imagine that much of our findings will illustrate how the cell cycle is regulated in larger eukaryotic organisms.
M604B Medical Sciences Bldg.
Columbia, MO 65212
- Genetics of Saccharomyces cerevisiae
- Role of protein phosphatase in cell cycle regulation
Areas of Expertise
- Cancer Biology
- Cell Biology
- Signal Transduction
Education & Training
1983, PhD, University of Wisconsin-Madison
- Ghosh, A and J Cannon. 2013. Analysis of protein phosphatase-1 and aurora protein kinase suppressors reveals new aspects of regulatory protein function in Saccharomyces cerevisiae PLoS One. 2013 Jul 22;8(7):e69133. doi: 10.1371/journal.pone.0069133
- Cannon, JF. 2012. How phosphorylation activates the protein phosphatase-1 • inhibitor-2 complex. Biochim Biophys Acta. 1834:71-86.
- Cannon, JF. 2010. Function of protein phosphatase-1, Glc7, in Saccharomyces cerevisiae. Adv. App. Microbiol. 73: 27-58.
- Thamburan, S., Klaasen, J., Mabusela, WT, Cannon JF, Folk, W, and Q Johnson. 2006. Tulbaghia alliacea phytotherapy: A potential anti-infective remedy for candidiasis. Phytother Res 20: 844-850.
- Tan YS, PA Morcos, and JF Cannon. 2003. Pho85 phosphorylates the glc7 protein phosphatase regulator glc8 in vivo. J Biol Chem. 278(1):147-153.
- Nigavekar SS, YS Tan, and JF Cannon. 2002. Glc8 is a glucose-repressible activator of Glc7 protein phosphatase-1. Arch Biochem Biophys. 404(1):71-79.
- Nigavekar S and JF Cannon. 2002. Characterization of genes that are synthetically lethal with ade3 or leu2 in Saccharomyces cerevisiae. Yeast. 19:115-122.
- De Silva-Udawatta MN and JF Cannon. 2001. Roles of trehalose phosphate synthase in yeast glycogen metabolism and sporulation. Mol. Micro. 40:1345-1356.
- Zheng J, M Khalil and JF Cannon. 1999. Glc7p protein phosphatase inhibits expression of glutamine-fructose-6-phosphate transaminase from GFA1. J. Biol. Chem. 275:18070-18078.
- Ramaswamy N.T., L. Li, M. Khalil, JF Cannon. 1998. Regulation of yeast glycogen metabolism and sporulation by Glc7p protein phosphatase. Genetics. 149(1):57-72.
- Connor J.H., H.N. Quan, N.T. Ramaswamy, L. Zhang, S. Barik, J. Zheng, JF Cannon, E.Y. Lee, S. Shenolikar. 1998. Inhibitor-1 interaction domain that mediates the inhibition of protein phosphatase-1. J Biol Chem. 273(42):27716-27724.
- Dalley, B.K. and JF Cannon. 1996. Novel, activated RAS mutations alter protein-protein interactions. Oncogene. 13(6):1209-1220.