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Fig. 3. Defects associated with aberrant cell division can trigger cell death and might prevent proliferation of tetraploid cells. Defective kinetochores and microtubules (MTs), as well as disruption of centrosomes or the actin cytoskeleton, can initiate cell death. The mitotic-checkpoint proteins Bub1 and BubR1 might also trigger a post-mitotic, p53-dependent cell death after chromosome missegregation owing to spindle defects. The centrosomal kinase Lats2 inhibits p53 degradation by inhibiting Mdm2 in the absence of MTs, thus activating the apoptotic pathway. Disruption of centrosome integrity induces the p38 stress pathway, which can also trigger p53-dependent apoptosis. The experimental formation of tetraploid cells is frequently associated with disruption of the actin cytoskeleton. Cytoskeletal defects lead to disrupted focal adhesions, which, in their unimpaired state, are essential for cellular survival pathways because they can suppress the p38 stress pathway. p53 mediates apoptotic and cell-cycle-arresting signals by initiating the transcription of multiple effector proteins. It should be noted that the proposed pathways in this figure are not well established. For further details, see text.
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