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C R Mantel

Publications and source records attributed to C R Mantel.

8 recordsLinked to original sources
PubMed2001

The interphase microtubule damage checkpoint defines an S-phase commitment point and does not require p21(waf-1).

Cell cycle checkpoints ensure orderly progression of events during cell division. A microtubule damage (MTD)-induced checkpoint has been described in G(1) phase of the cell cycle (G(1)MTC) for which little is known. The present study shows that the G(1)MTC is intact in activated T lymphocytes from mice with the p21(waf-1) gene deleted. However, p21(waf-1) gene deletion does affect the ratio of cells that arrest at the G(1)MTC and the spindle checkpoint after MTD. The G(1)MTC arrests T lymphocytes in G(1) prior to cdc2 up-regulation and prior to G(1) arrest by p21(waf-1). Once cells have progressed past the G(1)MTC, they are committed to chromosome replication and metaphase progression, even with extreme MTD. The G(1)MTC is also present in a human myeloid cell line deficient in p21(waf-1) gene expression. The p21-independent G(1)MTC may be important in cellular responses to MTD such as those induced by drugs used to treat cancer.

Animals↗
PubMed2000

An expansion phase precedes terminal erythroid differentiation of hematopoietic progenitor cells from cord blood in vitro and is associated with up-regulation of cyclin E and cyclin-dependent kinase 2.

The dynamics of cell cycle regulation were investigated during in vitro erythroid proliferation and differentiation of CD34(+) cord blood cells. An unusual cell cycle profile with a majority of cells in S phase (70.2%) and minority of cells in G1 phase (27.4%) was observed in burst-forming unit-erythrocytes (BFU-E)-derived erythroblasts from a 7-day culture of CD34(+) cells stimulated with interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), Steel factor, and Epo. Terminal erythroid differentiation was accompanied by a rapid increase of G0/G1 phase cells. Expression of cyclin E and cyclin-dependent kinase 2 (cdk2) correlated with the proportion of S phase cells. Cyclin D3 was moderately up-regulated during the proliferation phase, and both cyclin E and D3 were rapidly down-regulated during terminal differentiation. This suggests that the high proliferation potential of erythroblasts is associated with temporal up-regulation of cyclin E and cdk2. (Blood. 2000;96:3985-3987)

CDC2-CDC28 Kinases↗
PubMed1997

Biology and mechanisms of action of synergistically stimulated myeloid progenitor cell proliferation and suppression by chemokines.

A number of cytokines can act together to stimulate/enhance the proliferation of hematopoietic stem and progenitor cells in a greater than additive fashion. An example of this is the combination of a colony-stimulating factor with a potent costimulating molecule such as steel factor. Certain members of the chemokine family of cytokines can suppress this synergistically enhanced proliferation. This review focuses on cytokines involved in these stimulating/enhancing/suppressing effects with regard to biological activity and what is beginning to be learned about the intracellular signal transduction events that may be mediating these effects. Examples of intracellular mediators involved include, but are not limited to, the Raf-1/ MAP kinase pathway and cyclin-dependent kinase inhibitors p21cip-1 and p27kip-1 for cell proliferation, and eukaryotic initiation factor-4E and 4E binding protein 1 for protein synthesis.

Animals↗
PubMed1993

Kinetic selectivity of cholinephosphotransferase in mouse liver: the Km for CDP-choline depends on diacylglycerol structure.

The effects of different 1,2-diacyl-sn-glycerols on the kinetic properties of CDP-choline:1,2-diacylglycerol cholinephosphotransferase (EC 2.7.8.2) from mouse liver microsomes have been studied. Initial-velocity experiments were carried out with various concentrations of several species of diacylglycerol at different fixed concentrations of CDP-choline. Kinetic analysis of these data showed a family of intersecting lines consistent with a sequential kinetic mechanism of catalysis. The Km and Vmax. values derived from rate data revealed a pronounced effect of diacylglycerol species utilization on the Km value for CDP-choline. There was a biphasic relationship between diacylglycerol chain length and the Km for CDP-choline. Substitution of an unsaturated fatty acid in the sn-2 position of distearin also dramatically increased the CDP-choline Km value as well as the Vmax. 1,2-Dipalmitoyl-sn-glycerol was the preferred substrate over other disaturated species, but 1,2-dihexanoyl-sn-glycerol could not be utilized. These results demonstrate the kinetic mechanism of in vitro catalysis and suggest a regulatory role for CDP-choline concentration in the diacylglycerol species selectivity of cholinephosphotransferase resulting in the de novo biosynthesis of different molecular species of phosphatidylcholine.

Animals↗