E cyclins

Figure 1 Overview of the different phases of the cell cycle. Quiescent cells are in GO phase and reenter the cell cycle at Gl during which cells prepare for DNA synthesis. After passing the restriction point in late Gl cells are committed to enter S phase, during which DNA replication occurs. Cells in G2 phase prepare for mitosis (M phase). Cell cycle progression is controlled by various positive and negative cell cycle regulatory proteins including cyclins (A, B, D, E) cyclin dependent kinases (cdk 1,2, 4, 6) cdk inhibitors (p15, p16, p18, p19, p21, p27, p57), retinoblastoma (Rb) and p53.

The hyper-proliferation of tumor is a highly regulated process that progresses like normal cells through the four phases of cell cycle - Gl, S, G2, and M - which are controlled by cell cycle regulatory proteins. These include cyclins (cyclin A, B, Ds, or E), cyclin-dependent kinase (CDK CDKl, 2, 4, or 6), and associated CDK inhibitors (CKI) such as p27 p53, and phosphorylated retino-... 

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De Bondt, H.E., et al. Crystal structure of cyclin-depen-dent kinase 2. Nature 363 595-602, 1993. 

Othet cyclins and CDKs are involved in different aspects of cell cycle progression (Table 36-7). Cychn E and CDK2 form a complex in late Gl. Cychn E is tapidly degraded, and the released CDK2 then fotms a complex with cyclin A. This sequence is necessaty fot the initiation of DNA synthesis in S phase. A complex between cychn B and CDKl is tate-hmiting fot the G2/M transition in eukatyotic cells. 

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Evans, T., Rosenthal, E. T Youngblom, J., Distel, D., and Hunt, T. (1983). Cyclin a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33 389-396. 

Koff, A., Cross, F., Fisher, A., Schumacher, J Leguellec, K Philippe, M., and Roberts, J. M. (1991). Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell 66 1217-1228. 

Tsai, L-H., Harlow, E., and Meyerson, M. (1991). Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus ElA-associated p33 kinase. Nature 353 174-177. 

Whitfield, W. G. F., Gonzalez, C., Sanchez-Herrero, E., and Glover, D. M. (1989). Transcripts of one of two Drosophila cyclin genes become localized in pole cells during embryogenesis. Nature 338 337-340. 

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