Protein kinase C encodes a family of enzymes implicated in cellular di erentiation, growth control and tumor promotion. However, not much is known with respect to the molecular mechanisms that link protein kinase C to cell cycle control. Here we report that the expression of PKCZ in MCF-7 cells, under the control of a tetracycline-responsive inducible promoter, enhanced cell growth and a ected the cell cycle at several points. The induced expression of another PKC isoform, PKCd, in MCF-7 cells had opposite e ects and inhibited their growth. PKCZ expression activated cellular pathways in these cells that resulted in the increased expression of the G1 phase cyclins, cyclin D and cyclin E. Expression of the cyclin-dependent kinase inhibitor p21 WAF1 was also speci®cally elevated in PKCZ expressing cells, but its overall e ects were not inhibitory. Although, the protein levels of the cyclin-dependent kinase inhibitor p27 KIP1 were not altered by the induced expression of PKCZ, the cyclin E associated Cdk2 kinase activity was in correlation with the p27 KIP1 bound to the cyclin E complex and not by p21 WAF1 binding. PKCZ expression enhanced the removal of p27 KIP1 from this complex, and its re-association with the cyclin D/Cdk4 complex. Reduced binding of p27 KIP1 to the cyclin D/Cdk4 complex at early time points of the cell cycle also enhanced the activity of this complex, while at later time points the decrease in bound p21 WAF1 correlated with its increased activity in PKCZ-expressing cells. Thus, PKCZ induces altered expression of several cell cycle functions, which may contribute to its ability to a ect cell growth. Oncogene (2001) 20, 6794 ± 6804.
No abstract
We investigate the final stage of cytokinesis in two types of amoeba, pointing out the existence of biphasic furrow contraction. The first phase is characterized by a constant contraction rate, is better studied, and seems universal to a large extent. The second phase is more diverse. In Dictyostelium discoideum the transition involves a change in the rate of contraction, and occurs when the width of the cleavage furrow is comparable to the height of the cell. In Entamoeba invadens the con-tractile ring carries the cell through the first phase, but cannot complete the second stage of cytokinesis. As a result, a cooperative mechanism has evolved in that organism, where a neighboring amoeba performs directed motion towards the dividing cell, and physically causes separation by means of extending a pseudopod. We expand here on a previous report of this novel chemotactic signaling mechanism.
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