Previously studies on p27, cyclin kinase inhibitors, have been shown that p27 related to cell proliferation and differentiation. However, The experiment result from the study group of Stuart J. Shankland suggested that p27 played a double sward role in cell programmed death. p27-/- cells could lead to decrease CDK2 activity. The apoptosis was not detected in serum-starved transfected p27 â€/†cells transfected with the p27 plasmid while detected in nontransfected cells.p27 mutant plasmid transfected cells does not bind CDK2 and GFP, also, no cell programmed death was detected. TUNEL method has been used during this study, the staining was detected in antisense oligonucleotides (to p27) transfected cells. WB analysis showed that,CDK2 activity was increased in p27-/- mesangial cells and p27-/- fibroblasts in contrast with p27+/+ cells. the activity of CDK2 was remained increase at 6h and 18h after growth factor deprivation in p27-/-cells compared with p27+/+ cells, and CDK2 remained on protein levels in this experiment. Quantitation of CDK2 kinase activity was detected. In p27 â€/†and p27 +/+ cells, cyclin Eâ€CDK2 and cyclin Aâ€CDK2 activity were increased. However, in p27 â€/†mesangial cells, cyclin Aâ€CDK2 activity, but not cyclinEâ€CDK2 activity, remained increased after growth factor deprivation. All in all, this study suggested that p27 has two biological functions, preventing cell death and accelerating proliferation. The function of p27 was different under certain condition. Mounts of evidence shows that cyclin-dependent kinase (CDK) inhibitors of the Cip/Kip family, including p57Kip2 and p27Kip1, regulate not only cell cycle exit but also the corticogenesis. However, the activities of p57Kip2 protein are poorly identified . In cell culture and vivo, Anna Tury.et al find p57Kip2 over expresses at E14.5â€15.5 elicite cell cycle exit, promote the transition from proliferation to neuronal differentiation, and enhance the process outgrowth, while opposite effects happen in precursors which is inadequate of p57Kip2.Later research show the overexpression of p57Kip2 stimulates precocious glial differentiation, exhibiting stage dependent effects. In embryonic cortex, p57Kip2 over-expression, promotes cell migration and changes in postnatal radial layer positioning. Although the two CKIs, both p57Kip2 and p27Kip1 take part in the induction of differentiation, p57Kip2 have twice effective in induction of neuronal differentiation as p27Kip1 and intolerant of astrogliogenic effect of ciliary neurotrophic factor, showing that, CKIs difference in regulation of cell fate decisions. At the molecular level, although the highly conserved N - terminal region drives the cell cycle withdrawal and differentiation, , C - terminal region of the p57Kip2 alone inhibits the migration. In addition, the effect of neurogenesis and gliogenesis of p57Kip2 requires N - terminal cyclin / CDK binding / inhibitory areas, while the previous study shows p27Kip1 cell cycle-independent functions. These research suggest p57Kip2 coordinates multiple stages, and compared to p27Kip1, the related family members, exhibit different activities. Related References: Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27 Related Posts Review: p57Kip2, CDKs inhibitor, regulates cell cycle exit, differentiation, and migration of Embryonic Cerebral Cortical Precursors
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