Calyculin A from Discodermia calyx is a dual action toxin that blocks calcium influx and inhibits protein Ser/Thr phosphatases.
Calyculin A from Discodermia calyx is a dual action toxin that blocks calcium influx and inhibits protein Ser/Thr phosphatases.
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DOI：
10.3390/toxins4100940
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发表时间：
2012-10
期刊：
影响因子：
4.2
通讯作者：
Brautigan DL
中科院分区：
文献类型：
--
作者：
Holy M;Brautigan DL
Calyculin A（Caly A）是一种细胞穿透性毒素，作为PPP家族1型和2A型蛋白质Ser/Thr磷酸酶的抑制剂，广泛应用于细胞生物学研究。在这里，我们测试了低浓度的Caly A对人类癌症和非癌细胞系增殖的影响。我们发现，长期0.3 nM Caly A可阻止人Hs-68成纤维细胞和ARPE 19上皮细胞的G1期至S期细胞周期进展，但对人乳腺癌MDA-MB-468、MDA-MB-231和MCF 7细胞无效。这些条件没有产生细胞周期蛋白D1水平或内源性蛋白磷酸化的变化。然而，0.3 nM Caly A的急性应用阻断了Hs-68成纤维细胞中血清诱导的细胞内钙水平的增加，但在MDA-MB-468乳腺癌细胞中没有。我们认为，亚纳摩尔Caly A阻止细胞周期的进展，因为它阻止成纤维细胞的钙摄取。这可能涉及非选择性阳离子通道，癌细胞增殖不受影响，因为钙通过其他通道进入这些细胞。我们的研究结果表明，calyculin A具有双重作用，作为一个通道阻滞剂，除了其良好的磷酸酶抑制剂的影响。
Calyculin A (Caly A) is cell permeable toxin widely used in cell biology research as an inhibitor of type 1 and type 2A protein Ser/Thr phosphatases of the PPP family. Here we tested effects of low concentrations of Caly A on proliferation of human cancer and non-cancer cell lines. We found that long-term 0.3 nM Caly A prevented G1 to S phase cell cycle progression in human Hs-68 fibroblasts and ARPE19 epithelial cells, but not human breast cancer MDA-MB-468, MDA-MB-231 and MCF7 cells. These conditions produced no change in cyclin D1 levels or in the phosphorylation of endogenous proteins. However, acute application of 0.3 nM Caly A blocked serum-induced increase in intracellular calcium levels in Hs-68 fibroblasts, but not in MDA-MB-468 breast cancer cells. We propose that subnanomolar Caly A prevents cell cycle progression because it blocks calcium uptake by fibroblasts. This probably involves non-selective cation channels and cancer cell proliferation was not affected because calcium enters these cells by other channels. Our results suggest that calyculin A has dual actions and acts as a channel blocker, in addition to its well-established effects as a phosphatase inhibitor.
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影响因子：
2.3
作者：
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通讯作者：
Stacey DW
影响因子：
4.8
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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影响因子：
3.3
作者：
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通讯作者：
Gumbiner, Barry M.