Hudson, John W.
PhD, York University
MSc, McMaster University
BSc, McMaster University
Cell Cycle, Sak/Plk4 kinase and the Plk family of mitotic regulators.
Biology Building - 217
Tel: 519-253-3000 ext. 2715
My laboratory is studying the role of Plk4 kinase (also known as Sak) in the cell cycle, DNA damage pathways. Recent research has shown that Plks are involved in tumour suppressor and/or oncogenic pathways and thus may be implicated in the progression of cancer. Plk4 is a member of the polo-like kinase (plk) family of mitotic regulators. Plks control the cell cycle through the regulation of centrosome duplication, the anaphase-promoting complex (APC), DNA damage checkpoints, spindle formation and cytokinesis. They share a common domain architecture consisting of an N-terminal catalytic and one or two characteristic C-terminal motifs termed polo boxes (pb). Plk4 differs from the other plk family members in that it has only one pb domain. During the cell cycle, Plks localize to different cellular structures in a pattern that corresponds to the observations that plks perform different functions at different stages of the cell cycle. The similarity of polo kinase sequences, patterns of gene expression, and phenotypes when over-expressed or depleted suggest a critical role for plks in regulation of mitosis and meiosis.
Plk4 is necessary for completion of mitosis: Plk4 homozygous null mice are embryonic lethal at E7.5 with a marked increase in mitotic and apoptotic cells compared to wild type embryos. Null embryos display cells in late telophase and anaphase that continue to express cyclin B1 and phosphorylated histone H3. These results implicate Plk4 with a role in chromosomal segregation and exit from mitosis. Interestingly, aged
Plk4 heterozygous mice develop liver and lung tumours at a higher frequency (30%) than wild-type littermates (5%). In addition, murine embryonic fibroblasts (MEFs) derived from Plk4 heterozygous embryos have altered cell cycle profiles and proliferate at a slower rate than wild-type MEFs.
Our current research will provide a better understanding of the role of Plk4 in the cell cycle and cancer progression.
Potential Projects for New Students
Current Lab Members
Alex Ward (PhD Candidate)
Former Lab Members
Bing Wu MSc
Steve Petrinac MSc
Alan Morettin MSc
Sepal Bonni, MSc
Melissa L. Ganuelas, MSc
Kozarova A, Hudson JW, and Vacratsis PO. (2011) The dual specificity phosphatase hYVH1 (DUSP12) is a novel modulator of cellular DNA content. Cell Cycle. in press.
Ward A, Morettin A, Shum D, and Hudson JW. (2011) Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice. BMC Cancer 2011, 11:71
Morettin A, Ward A, Nantais J, and Hudson JW (2009). Gene expression patterns in heterozygous Plk4 Murine Embryonic Fibroblasts. BMC Genomics 10:319
Petrinac S, Ganuelas ML, Bonni S, Nantais J, and Hudson JW (2009). Polo-like kinase 4 Phosphorylates Chk2. Cell Cycle,8(2):327-9.
Raturi A, Miersch S, Hudson JW, and Mutus B (2008). Platelet microparticle-associated protein disulfide isomerase promotes platelet aggregation and inactivates insulin. Biochim Biophys Acta 1778(12):2790-6
Bonni S, Ganuelas ML, Petrinac S, and Hudson JW. (2008). Human Plk4 Phosphorylates Cdc25C. Cell Cycle,7(4):545-7.
Kozarova, A, Petrinac, S, Ali, A, and Hudson, JW. (2006). Array of Informatics: Applications in Modern Research. Journal of Proteome Research5(5):1051-9.
Ko, MA, Rosario, CO, Hudson, JW, Kulkarni, S, Pollett, A, Dennis, JW, Swallow, CJ (2005). Sak/Plk4 haplo-insufficiency causes mitotic infidelity and carcinogenesis. Nature Genetics37: 883-888.
Swallow, CJ, Ko, MA, Siddiqui, NU, Hudson, JW, Dennis, JW. (2005). Sak/Plk4 and mitotic fidelity. Oncogene 24(2):306-12.
Leung, GC, Hudson, JW, Kozarova, A, Davidson A, Dennis, JW and Sicheri, F. (2002). The Sak polo-box comprises a structural domain sufficient for mitotic subcellular localization. Nature Structural Biology 9: 719-724
Macmillan, JC, Hudson, JW, Dennis, JW and Swallow, CJ. (2001). Comparative expression of the mitotic regulators Sak and Plk in colorectal cancer. Ann. Surg. Oncol. 8(9):729-40.
Hudson, JW, Kozarova, A, Cheung P, Macmillan, JC, Swallow, CJ, Cross, JC and Dennis, JW. (2001). Late Mitotic Failure in Mice Lacking Sak, a Polo-like Kinase. Current Biology 11:441-446
Hudson, JW, Chen, L-Y, Fode, C, Binkert, C and Dennis, JW. (2000). Sak kinase Gene Structure and Transcriptional Regulation. Gene 241: 65-73
Varmuza S, Jurisicova A, Okano K, Hudson J, Boekelheide K, Shipp EB. (1999). Spermiogenesis is impaired in mice bearing a targeted mutation in the protein phosphatase 1cgamma gene. Dev Biol.205(1):98-110.