Cadmium is a potent inhibitor of PPM phosphatases and targets the M1 binding site.
Cadmium is a potent inhibitor of PPM phosphatases and targets the M1 binding site.
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镉是 PPM 磷酸酶的有效抑制剂，并针对 M1 结合位点
DOI：
10.1038/srep02333
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发表时间：
2013
影响因子：
4.6
通讯作者：
Sun, Jin-Peng
中科院分区：
文献类型：
--
作者：
Pan, Chang;Liu, Hong-Da;Gong, Zheng;Yu, Xiao;Hou, Xu-Ben;Xie, Di-Dong;Zhu, Xi-Bin;Li, Hao-Wen;Tang, Jun-Yi;Xu, Yun-Fei;Yu, Jia-Qi;Zhang, Lian-Ying;Fang, Hao;Xiao, Kun-Hong;Chen, Yu-Guo;Wang, Jiang-Yun;Pang, Qi;Chen, Wei;Sun, Jin-Peng
重金属镉是一种不可降解的污染物。通过筛选一组金属离子对磷酸酶活性的影响，我们意外地确定镉作为PPM1A和PPM1G的有效抑制剂。与此相反，低微摩尔浓度的镉没有抑制PP1或酪氨酸磷酸酶。动力学研究表明，镉通过M1金属离子结合位点抑制PPM磷酸酶。特别地，PPM1G中带负电荷的D441特异性地识别镉。我们的研究结果表明，镉可能是一个有效的抑制剂，大多数PPM家族成员除了PHLPPs。此外，我们证明镉在体内有效地抑制PPM 1A调节的MAPK信号和PPM 1G调节的AKT信号。镉逆转了PPM 1A诱导的细胞周期停滞，镉不敏感的PPM 1A突变体挽救了镉诱导的细胞死亡。总之，这些发现提供了一个更好地了解镉的毒性在人体生理学和病理学的背景下的影响。
The heavy metal cadmium is a non-degradable pollutant. By screening the effects of a panel of metal ions on the phosphatase activity, we unexpectedly identified cadmium as a potent inhibitor of PPM1A and PPM1G. In contrast, low micromolar concentrations of cadmium did not inhibit PP1 or tyrosine phosphatases. Kinetic studies revealed that cadmium inhibits PPM phosphatases through the M1 metal ion binding site. In particular, the negative charged D441 in PPM1G specific recognized cadmium. Our results suggest that cadmium is likely a potent inhibitor of most PPM family members except for PHLPPs. Furthermore, we demonstrated that cadmium inhibits PPM1A-regulated MAPK signaling and PPM1G-regulated AKT signaling potentlyin vivo. Cadmium reversed PPM1A-induced cell cycle arrest and cadmium insensitive PPM1A mutant rescued cadmium induced cell death. Taken together, these findings provide a better understanding of the effects of the toxicity of cadmium in the contexts of human physiology and pathology.
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影响因子：
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作者：
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通讯作者：
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作者：
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Yu X
影响因子：
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