CDK2 activity

Gu, Y., Rosenblatt, J., and Morgan, D. O. (1992). Cell cycle regulation of CDK2 activity by phosphorylation of Thrl61 and Tyrl5. EMBO J. 11 3995-4005. 

Cdk1 activity + periodic CycE/Cdk2 activity... 

Oncogene-transformed mouse fibroblasts have a more decondensed chromatin structure than parental cell lines [59]. Phosphorylated Hl -3 levels are elevated in oncogene (ras, raf, fes, mos, myc) and aberrantly expressed MAPKK (MEK) transformed mouse fibroblasts, which have elevated activities of MAPK (ERKl and 2) [59] (Fig. 6). Further, RZ)-deficient human fibroblasts have increased levels of phosphorylated HI and a relaxed chromatin structure [60]. Cyclin E-Cdk2 was directly involved in increasing the levels of phosphorylated HI [60]. Elevated cyclin E-Cdk2 activity resulting from persistent activation of the Ras-MAPK pathway is also responsible for increased level of phosphorylated HI in oncogene-transformed mouse fibroblasts [61]. 

Figure 3. Oncogenic potential of ubiquitin ligases. MDM2 and Skp2 regulate levels of the tumor suppressors p53 and p27, respectively. Deregulated degradation of p53 and p27 results in cyclin E/cdk2 activation and cell proliferation.

Nguyen, H., Gitig, D. M., and Koff, A. (1999). Cell-free degradation of p27(kipl), a G1 cyclin-dependent kinase inhibitor, is dependent on CDK2 activity and the proteasome. Mol Cell Biol 19, 1190-1201. 

FIGURE 12-43 Variations in the activities of specific CDKs during the cell cycle in animals. Cyclin E-CDK2 activity peaks near the G1 phase-S phase boundary, when the active enzyme triggers synthesis of enzymes required for DNA synthesis (see Fig. 12-46). Cyclin A-CDK2 activity rises during the S and G2 phases, then drops sharply in the M phase, as cyclin B-CDK1 peaks. 

Fig. 9.6 Retrieval rates using three-point fingerprints for FGF and CDK2 actives using FGF as the target protein.

PKC activation [antitumour, PKC activation downregulation, CDK2 activity suppression, cell cycle arrest]... 

The petroleum ether extract of Panax ginseng has antiproliferative effects on various cancer cell lines (murine sarcoma, murine leukaemia, human colon carcinoma, etc ). Polyacetylenic compounds from this extract such as panaxynol, panaxydol (46) and panaxytriol have been reported to be responsible for these effects [112, 113]. In order to identify the molecular mechanism of the polyacetylene compounds, one of the major cytotoxic compounds, panaxydol, was examined to see if it is able to disrupt cell cycle-related events. It was observed that panaxydol induces cell cycle arrest at Gi-S transition in SK-MEL-1 cells. This effect is related to the decreased Cdk2 activity, which seems to be caused by the increased level of p27 protein expression. The protein synthesis inhibitor cycloheximide reversed the growth suppression induced by panaxydol (80 j,g/ml) by... 

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