Within minutes of fertilization, clam embryos begin to make several new proteins, some of which are absolutely essential for progress through the cell cycle and entry into mitosis. Two of these proteins, cyclin A and cyclin B, appear to be regulators of mitosis. They accumulate across the cell cycle and are abruptly destroyed near the end of each mitosis. Direct evidence shows that the rise in cyclin A can induce mitosis; indirect evidence suggests that cyclin B lead to exit from mitosis. The long term goals of this project are to understand the roles of the cyclins in the cell cycles of early embryos and to investigate their functions in somatic cell cycles of vertebrates. (1) Immunofluorescence techniques will be used to visualize the intracellular distributions of the cyclins as cell proceed through the cell cycle. (2) Antibodies and purified cyclin proteins will be used to study the relationship between the cyclins and MPF (M phase Promoting Factor), a key regulator of the cell cycle that has eluded purification and molecular characterizations since its discovery almost twenty years ago. (3) Cell-free systems will be used to identify the specific mitotic processes that are controlled or influenced by the cyclins. (4) Existing and new antibodies and DNA probes will be used to search for cyclin proteins and genes in somatic cells. This work should identify important regulatory steps that control the cell cycle at the G2/M transition and it may reveal new kinds of regulatory mechanisms in somatic cells.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD023696-05
Application #
3323882
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1989-09-01
Project End
1993-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Miduturu, Chandrasekhar V; Deng, Xianming; Kwiatkowski, Nicholas et al. (2011) High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors. Chem Biol 18:868-79
Gadea, Bedrick B; Ruderman, Joan V (2006) Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin. Proc Natl Acad Sci U S A 103:4493-8
Liu, Quentin; Ruderman, Joan V (2006) Aurora A, mitotic entry, and spindle bipolarity. Proc Natl Acad Sci U S A 103:5811-6
Selenko, Philipp; Serber, Zach; Gadea, Bedrick et al. (2006) Quantitative NMR analysis of the protein G B1 domain in Xenopus laevis egg extracts and intact oocytes. Proc Natl Acad Sci U S A 103:11904-9
Stanford, Jennifer S; Ruderman, Joan V (2005) Changes in regulatory phosphorylation of Cdc25C Ser287 and Wee1 Ser549 during normal cell cycle progression and checkpoint arrests. Mol Biol Cell 16:5749-60
Gadea, Bedrick B; Ruderman, Joan V (2005) Aurora kinase inhibitor ZM447439 blocks chromosome-induced spindle assembly, the completion of chromosome condensation, and the establishment of the spindle integrity checkpoint in Xenopus egg extracts. Mol Biol Cell 16:1305-18
Crane, Richard; Kloepfer, Angela; Ruderman, Joan V (2004) Requirements for the destruction of human Aurora-A. J Cell Sci 117:5975-83
Tsai, Ming-Ying; Wiese, Christiane; Cao, Kan et al. (2003) A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. Nat Cell Biol 5:242-8
Yam, C H; Siu, W Y; Kaganovich, D et al. (2001) Cleavage of cyclin A at R70/R71 by the bacterial protease OmpT. Proc Natl Acad Sci U S A 98:497-501
Farruggio, D C; Townsley, F M; Ruderman, J V (1999) Cdc20 associates with the kinase aurora2/Aik. Proc Natl Acad Sci U S A 96:7306-11

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