The long-range goal of this research is to understand the molecular basis of cell proliferation and how it is deranged in cancer cells. The focus of the grant is on the molecular and biochemical aspects of cell cycle control during exit from mitosis. The unfertilized eggs of vertebrates are arrested in metaphase by an activity known as cytostatic factor (CSF). CSF arrest can be elicited by expression of components of the MAPK pathway, including the MAPK substrate p9ORsk. p90Rsk phosphorylates and activates the spindle assembly checkpoint component Bub1. Bub1 activity has been linked to inhibition of the anaphase-promoting complex, which targets key proteins for degradation at the metaphase/anaphase transition. Experiments will evaluate whether Bub1 mediates CSF arrest by the MAPK pathway. This work provides a link between the MAPK/Rsk pathway and checkpoint control of the cell cycle at the metaphase/anaphase transition.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Cell Development and Function Integrated Review Group (CDF)
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Blondel, Olivier
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University of Colorado Denver
Schools of Medicine
United States
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Silverman, Eran; Frodin, Morten; Gammeltoft, Steen et al. (2004) Activation of p90 Rsk1 is sufficient for differentiation of PC12 cells. Mol Cell Biol 24:10573-83
Eyers, Patrick A; Maller, James L (2004) Regulation of Xenopus Aurora A activation by TPX2. J Biol Chem 279:9008-15
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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
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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

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