This research is designed to elucidate the molecular basis of the control of cell cycle proliferation. Increased understanding in this area will have important ramifications for understanding early embryonic development and the process of cancer. The work is oriented to understanding the transition from G2 to M phase in the cell cycle. We have purified and characterized the central control element in eucaryotic cells that control the G2 to M transition. This control element, known as M-phase promoting factor or MPF, is a complex between a 34 kDa protein kinase and a 45 kDa substrate. The protein kinase is a homolog of the cdc 2+ gene, termed p34cdc2 and the 45 kDa component is a cyclin that becomes phosphorylated and thiophosphorylated by p34cdc2. The p34cdc2 component is inactivated by phosphorylation. We propose to purify and characterize the protein kinases that act on p34cdc2, and determine the effect of cyclin phosphorylation on its stability and ability to associated p34cdc2. The pp60c-src proto- oncogene has been identified as a substrate of MPF, and the activation and inactivation of c-src during the cell cycle will be studied in relation to its phosphorylation by MPF. The regulation of lamin kinase activity will also be studied during the cell cycle regulation by MPF. These studies will advance fundamental knowledge about the cell cycle in terms of both how MPF activity is regulated and how MPF is actually able to cause nuclear events to occur via protein phosphorylation. The network between MPF and proto-oncogenes like c-src provides a novel basis for investigating the interface between cell cycle control and cell growth control.
| Liu, Junjun; Maller, James L (2005) Xenopus Polo-like kinase Plx1: a multifunctional mitotic kinase. Oncogene 24:238-47 |
| Eyers, Patrick A; Liu, Junjun; Hayashi, Nobuhiro R et al. (2005) Regulation of the G(2)/M transition in Xenopus oocytes by the cAMP-dependent protein kinase. J Biol Chem 280:24339-46 |
| Liu, Junjun; Lewellyn, Andrea L; Chen, Lin G et al. (2004) The polo box is required for multiple functions of Plx1 in mitosis. J Biol Chem 279:21367-73 |
| Conn, Christopher W; Lewellyn, Andrea L; Maller, James L (2004) The DNA damage checkpoint in embryonic cell cycles is dependent on the DNA-to-cytoplasmic ratio. Dev Cell 7:275-81 |
| Erikson, Eleanor; Haystead, Timothy A J; Qian, Yue-Wei et al. (2004) A feedback loop in the polo-like kinase activation pathway. J Biol Chem 279:32219-24 |
| Ionov, Yurij; Le, Xuan; Tunquist, Brian J et al. (2003) Pim-1 protein kinase is nuclear in Burkitt's lymphoma: nuclear localization is necessary for its biologic effects. Anticancer Res 23:167-78 |
| Maller, James L; Schwab, Markus S; Gross, Stefan D et al. (2002) The mechanism of CSF arrest in vertebrate oocytes. Mol Cell Endocrinol 187:173-8 |
| Qian, Y W; Erikson, E; Taieb, F E et al. (2001) The polo-like kinase Plx1 is required for activation of the phosphatase Cdc25C and cyclin B-Cdc2 in Xenopus oocytes. Mol Biol Cell 12:1791-9 |
| Maller, J L; Schwab, M S; Roberts, B T et al. (2001) The pathway of MAP kinase mediation of CSF arrest in Xenopus oocytes. Biol Cell 93:27-33 |
| Maller, J L; Gross, S D; Schwab, M S et al. (2001) Cell cycle transitions in early Xenopus development. Novartis Found Symp 237:58-73; discussion 73-8 |
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