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Int J Oncol. 1994 Apr;4(4):803-8.

Use of the cyclin e restriction point to map cell arrest in g(1)-induced by N-butyrate, cycloheximide, staurosporine, lovastatin, mimosine and quercetin.

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1
NEW YORK MED COLL,CANC RES INST,VALHALLA,NY 10595.

Abstract

Cyclin E, a member of the G1 cyclin family, is an integral component of the complex machinery of the cell cycle. This protein is synthesized late in the G1 phase of the cycle and its transient association with p33cdk2 is essential for cell entrance to S phase. Using bivariate DNA content - cyclin E expression flow cytometric analysis, we have compared the point of action in G1 of several agents with diverse mechanisms of action in terms of its relationship to the cyclin E restriction point: cell arrest prior to the onset of cyclin E synthesis was expected to result in accumulation of cyclin E negative cells (G1cyE-) whereas arrest past this point was expected to result in accumulation of G1 cells with an increased cyclin E content (G1cyE+). Incubation of MOLT-4 cells with n-butyrate (which induces hyperacetylation of histones and hypophosphorylation of histone H1) and the protein synthesis inhibitor cycloheximide arrested them in G1cyE. Likewise. incubation of c-ras transformed bladder carcinoma T24 cells with lovastatin (presumed to interfere with isoprenylation of p21ras and thus affecting the signal transduction pathway), or normal mitogen stimulated human lymphocytes with staurosporine (a protein kinase inhibitor) led to cell arrest in G1cyE. In contrast, growth of MOLT-4 cells in the presence of the bioflavonoid quercetin or plant amino acid mimosine, resulted in their arrest at the G, point past the onset of cyclin E synthesis (G1cyE+). Mapping the point(s) of action of drugs that perturb progression in the cycle with respect to the onset of synthesis of cyclin proteins offers some advantages compared to temporal mapping; the latter may vary due to intrinsic differences between cell types in the duration of G1, the induction of unbalanced growth, etc.

PMID:
21566985
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