Cyclin E activates Cdk2, controls centrosome duplication, and regulates histone gene transcription. Cyclin E is deregulated in cancer and appears as low-molecular-weight (LMW) isoforms that correlate strongly with decreased survival in breast cancer patients. Transgenic mice overexpressing LMW-cyclin E have increased incidence of mammary tumors and distant metastasis when compared with mice tha...

Cyclin E activates Cdk2, controls centrosome duplication, and regulates histone gene transcription. Cyclin E is deregulated in cancer and appears as low-molecular-weight (LMW) isoforms that correlate strongly with decreased survival in breast cancer patients. Transgenic mice overexpressing LMW-cyclin E have increased incidence of mammary tumors and distantmetastasis when compared withmice that ...

Thirteen novel cinnamamide-chalcone derivatives were synthesized and tested for their antiproliferative activity against MCF-7, K562, U-373MG, HT-29 cell lines using SRB assay. Eight compounds the in vitro CDK2 inhibition. Compounds 2g, 2h, 2k, 2l found to have IC50 < 10 µM CDK2. These four evaluated on EGFR kinase be two times more selective docked into Glide software. The docking studies reve...

Adaptive immunity requires signals from both the TCR and the costimulatory molecule CD28. These receptors activate multiple signaling pathways, including the cyclin-dependent kinase (CDK) cascade, and antigenic signals in the absence of costimulation result in a tolerant state that is enforced by the CDK inhibitory protein p27kip1. We find that CDK2, the major target of p27kip1, is highly activ...

RhoA has been identified as an important regulator of cell proliferation. We recently showed that the Ras/RhoA pathway regulates the degradation of p27(Kip) and the progression of Chinese hamster embryo fibroblasts (IIC9 cells) through G1 into S phase (Weber, J. D., Hu, W., Jefcoat, S. C., Raben, D. M., and Baldassare, J. J. (1997) J. Biol. Chem. 272, 32966-32971). In this report, we have demon...

The cyclin-dependent kinases (CDKs) that promote cell-cycle progression are targets for negative regulation by signals from damaged or unreplicated DNA, but also play active roles in response to DNA lesions. The requirement for activity in the face of DNA damage implies that there are mechanisms to insulate certain CDKs from checkpoint inhibition. It remains difficult, however, to assign precis...

Human cytomegalovirus (HCMV) stimulates numerous cellular pathways upon infection. One of these pathways involves activation of cyclin E/Cdk2. Recent reports have demonstrated that Cdk2 is retained in the cytoplasm of cells arrested in GO by serum deprivation, sequestered from its regulatory subunit cyclin E which is located within the nucleus. Cdk2 rapidly enters the nucleus and becomes active...

We have found that the replicative helicase E1 of bovine papillomavirus type 1 (BPV-1) interacts with a key cell cycle regulator of S phase, the cyclin E-Cdk2 kinase. The E1 helicase, which interacts with cyclin E and not with Cdk2, presents the highest affinity for catalytically active kinase complexes. In addition, E1, cyclin E, and Cdk2 expressed in Xenopus egg extracts are quantitatively co...

The 2.6 Angstrom crystal structure for human cyclin-dependent kinase 2(CDK2) in complex with CksHs1, a human homolog of essential yeast cell cycle-regulatory proteins suc1 and Cks1, reveals that CksHs1 binds via all four beta strands to the kinase C-terminal lobe. This interface is biologically critical, based upon mutational analysis, but far from the CDK2 N-terminal lobe, cyclin, and regulato...

In higher eukaryotes, Cdk2 kinase plays an essential role in regulating the G1-S transition. Here, we use cycling Xenopus egg extracts to examine the requirement of Cdk2 kinase on progression into mitosis. Interestingly, when Cdk2 kinase activity is inhibited by the Cdk-specific inhibitor, p21Cip1, a block to mitosis occurs, and inactive Cdc2-cyclin B accumulates. This block occurs in the absen...