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|Title:||p53-independent induction of p21waf1/cip1 contributes to the activation of caspases in GTP-depletion-induced apoptosis of insulin-secreting cells|
|Authors:||Huo, J.X. |
Pancreatic islet β-cells
|Citation:||Huo, J.X., Metz, S.A., Li, G.D. (2004-01). p53-independent induction of p21waf1/cip1 contributes to the activation of caspases in GTP-depletion-induced apoptosis of insulin-secreting cells. Cell Death and Differentiation 11 (1) : 99-109. ScholarBank@NUS Repository.|
|Abstract:||We investigated the role of some key regulators of cell cycle in the activation of caspases during apoptosis of insulin-secreting cells after sustained depletion of GTP by a specific inosine 5′-monophosphate dehydrogenase inhibitor, mycophenolic acid (MPA). p21Waf1/Cip1 was significantly increased following MPA treatment, an event closely correlated with the time course of caspase activation under the same conditions. MPA-induced p21Waf1/Cip1 was not mediated by p53, since p53 mass was gradually reduced over time of MPA treatment. The increment of p21Waf1/Cip1 by MPA was further enhanced in the presence of a pan-caspase inhibitor, indicating that the increased p21Waf1/Cip1 may occur prior to caspase activation. This notion of association of p21Waf1/Cip1 accumulation with caspase activation and apoptosis was substantiated by using mimosine, a selective p21Waf1/Cip1 inducer independent of p53. Mimosine, like MPA, also increased p21Waf1/Cip1, promoted apoptosis and simultaneously increased the activity of caspases. Furthermore, knocking down of p21Waf1/Cip1 transfection of siRNA duplex inhibited caspase activation and apoptosis due to GTP depletion. In contrast to p21Waf1/Cip1, a reduction in p27Kip1 occurred in MPA-treated cells. These results indicate that p21Waf1/Cip1 may act as an upstream signal to block mitogenesis and activate caspases which in turn contribute to induction of apoptosis.|
|Source Title:||Cell Death and Differentiation|
|Appears in Collections:||Staff Publications|
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