Search results for "Cyclin-dependent kinase 1"
showing 8 items of 18 documents
Type III Secretion-Dependent Cell Cycle Block Caused in HeLa Cells by Enteropathogenic Escherichia coliO103
2001
ABSTRACT Rabbit enteropathogenic Escherichia coli (EPEC) O103 induces in HeLa cells an irreversible cytopathic effect characterized by the recruitment of focal adhesions, formation of stress fibers, and inhibition of cell proliferation. We have characterized the modalities of the proliferation arrest and investigated its underlying mechanisms. We found that HeLa cells that were exposed to the rabbit EPEC O103 strain E22 progressively accumulated at 4C DNA content and did not enter mitosis. A significant proportion of the cells were able to reinitiate DNA synthesis without division, leading to 8C DNA content. This cell cycle inhibition by E22 was abrogated in mutants lacking EspA, -B, and -D…
High-throughput screening with the Eimeria tenella CDC2-related kinase2/cyclin complex EtCRK2/EtCYC3a
2012
The poultry disease coccidiosis, caused by infection with Eimeria spp. apicomplexan parasites, is responsible for enormous economic losses to the global poultry industry. The rapid increase of resistance to therapeutic agents, as well as the expense of vaccination with live attenuated vaccines, requires the development of new effective treatments for coccidiosis. Because of their key regulatory function in the eukaryotic cell cycle, cyclin-dependent kinases (CDKs) are prominent drug targets. The Eimeria tenella CDC2-related kinase 2 (EtCRK2) is a validated drug target that can be activated in vitro by the CDK activator XlRINGO (Xenopus laevis rapid inducer of G2/M progression in oocytes). B…
Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint. Involvement of the CHK2 kinase.
2001
AbstractThe bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1 dephosphorylation and activation. We report that upon CDT treatment CDC25C is fully sequestered in the cytoplasmic compartment, an effect that is reminiscent of DNA damage-dependent checkpoint activation. We show that the checkpoint kinase CHK2, an upstream regulator of CDC25C, is phosphorylated and activated after CDT treatment. In contrast to what is observed with other DNA damaging agents, we demonstrate that the activation of CHK2 can only take place during S-phase. Use of wortmannin and caffeine suggests that this effect is no…
The clinical significance of CDK1 expression in oral squamous cell carcinoma
2014
Objectives: To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK 1 ) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods. Study Design: Immunohistochemical expression of CDK 1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK 1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated. Results: The CDK 1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK 1 was significantly correlated with the histological grade of OSCC ( P <0.05).…
N-(INDAZOLYL)BENZAMIDO DERIVATIVES AS CDK1 INHIBITORS: DESIGN, SYNTHESIS, BIOLOGICAL ACTIVITY, AND MOLECULAR DOCKING STUDIES
2009
A series of N-1H-indazole-1-carboxamides has been synthesized and their effects on both CDK1/cyclin B and the K-562 (human chronic myelogenus leukemia) cell line were evaluated. Using a computational model, we have observed that all the most active compounds 9e, f, i-n exhibited the same binding mode of purvanalol A in the ATP-binding cleft. Although they were able to moderately inhibit the leukemic cell line K-562 and to show inhibitory activity against the Cdc2-Cyclin B kinase in the low micromolar range, they turned out to be non-cytotoxic against HuDe (IZSL) primary cell cultures from human derm. These preliminary results are quite encouraging in view of the low toxicity demonstrated by…
Functional distinction between Cln1p and Cln2p cyclins in the control of the Saccharomyces cerevisiae mitotic cycle.
2004
Abstract Cln1p and Cln2p are considered as equivalent cyclins on the basis of sequence homology, regulation, and functional studies. Here we describe a functional distinction between the Cln1p and Cln2p cyclins in the control of the G1/S transition. Inactivation of CLN2, but not of CLN1, leads to a larger-than-normal cell size, whereas overexpression of CLN2, but not of CLN1, results in smaller-than-normal cells. Furthermore, mild ectopic expression of CLN2, but not of CLN1, suppresses the lethality of swi4swi6 and cdc28 mutant strains. In the absence of Cln1p, the kinetics of budding, initiation of DNA replication, and activation of the Start-transcription program are not affected; by cont…
Localization of HSP70, Cdc2, and cyclin B in sea urchin oocytes in non-stressed conditions.
2003
In Paracentrotus lividus embryos, a Mediterranean sea urchin species, HSP70 is present in all the cells. During cell division it localizes under normal growth conditions on the centrosomes and on the whole isolated mitotic apparatus. Now, in situ hybridization, Western blot analyses, and immunohistochemistry show that the HSP70 mRNA is present in both small and large P. lividus oocytes, that all four isoforms of HSP70 can be found also in the oocytes, and that a certain amount of HSP70 localizes on asters and spindles during polar body formation. Moreover, two representative cell-cycle related proteins, cyclin B, and Cdc2, are present both in small and large oocytes, concentrating in the ge…
Phosphorylation of an Overexpressed Yeast Ras2 Protein During the G1 Phase of the Cell Cycle
1994
RAS proteins regulate growth and differentiation in evolutionarily distant systems such as vertebrates and yeast (for reviews, see Tamanoi, 1988; Gibbs and Marshall, 1989; Broach and Deschenes, 1990). At the moleular level, a key function of the yeast RAS1 and RAS2 proteins (collectively referred to as RAS) is to positively regulate the production of cyclic AMP at the onset of the G1 phase of the cell cycle (Toda et al., 1985; De Vendittis et al., 1986). At this stage, RAS proteins are transiently activated by the noncovalent binding of a GTP molecule. Reversal of the effect occurs by the hydrolytic splitting of the ’γ-phosphate of GTP, that leaves a functionally inactive RASGDP complex, th…