Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK028353-21
Application #
6622040
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Blondel, Olivier
Project Start
1981-03-01
Project End
2005-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
21
Fiscal Year
2003
Total Cost
$226,609
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

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
Tunquist, Brian J; Maller, James L (2003) Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs. Genes Dev 17:683-710
Tunquist, Brian J; Eyers, Patrick A; Chen, Lin G et al. (2003) Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest. J Cell Biol 163:1231-42
Eyers, Patrick A; Erikson, Eleanor; Chen, Lin G et al. (2003) A novel mechanism for activation of the protein kinase Aurora A. Curr Biol 13:691-7
Tunquist, Brian J; Schwab, Markus S; Chen, Lin G et al. (2002) The spindle checkpoint kinase bub1 and cyclin e/cdk2 both contribute to the establishment of meiotic metaphase arrest by cytostatic factor. Curr Biol 12:1027-33
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
Schwab, M S; Roberts, B T; Gross, S D et al. (2001) Bub1 is activated by the protein kinase p90(Rsk) during Xenopus oocyte maturation. Curr Biol 11:141-50
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

Showing the most recent 10 out of 41 publications