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蛋白磷酸酶4催化亚基的纯化:抗肿瘤药物福司曲星及其他肿瘤抑制因子和启动子的抑制作用

Purification of protein phosphatase 4 catalytic subunit: inhibition by the antitumour drug fostriecin and other tumour suppressors and promoters.

作者信息

Hastie C J, Cohen P T

机构信息

Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK.

出版信息

FEBS Lett. 1998 Jul 24;431(3):357-61. doi: 10.1016/s0014-5793(98)00775-3.

DOI:10.1016/s0014-5793(98)00775-3
PMID:9714542
Abstract

Protein phosphatase 4 (PP4) is a protein serine/threonine phosphatase that predominantly localises to centrosomes and plays a role in microtubule organisation at centrosomes. Here, PP4 catalytic subunit has been purified from porcine testis to near homogeneity and a specific activity of 680 mU/mg against phosphorylase alpha. The antitumour drug, fostriecin, inhibits PP4 catalytic subunit (IC50 3 nM) with similar potency to PP2A catalytic subunit (IC50 1.5 nM). PP4 is also inhibited in the nanomolar range by several naturally occurring tumour promoters and toxins, with similar IC50 values to those obtained for PP2A. The gene for human PP4 catalytic subunit localises to 16p11.2.

摘要

蛋白磷酸酶4(PP4)是一种蛋白丝氨酸/苏氨酸磷酸酶,主要定位于中心体,并在中心体的微管组织中发挥作用。在此,已从猪睾丸中纯化出PP4催化亚基,使其接近均一,并且对磷酸化酶α的比活性为680 mU/mg。抗肿瘤药物福司曲星抑制PP4催化亚基(IC50为3 nM),其效力与PP2A催化亚基(IC50为1.5 nM)相似。几种天然存在的肿瘤启动子和毒素也能在纳摩尔范围内抑制PP4,其IC50值与PP2A的相似。人PP4催化亚基的基因定位于16p11.2。

相似文献

1
Purification of protein phosphatase 4 catalytic subunit: inhibition by the antitumour drug fostriecin and other tumour suppressors and promoters.蛋白磷酸酶4催化亚基的纯化:抗肿瘤药物福司曲星及其他肿瘤抑制因子和启动子的抑制作用
FEBS Lett. 1998 Jul 24;431(3):357-61. doi: 10.1016/s0014-5793(98)00775-3.
2
Fostriecin, an antitumor antibiotic with inhibitory activity against serine/threonine protein phosphatases types 1 (PP1) and 2A (PP2A), is highly selective for PP2A.福司曲星是一种对1型丝氨酸/苏氨酸蛋白磷酸酶(PP1)和2A型丝氨酸/苏氨酸蛋白磷酸酶(PP2A)具有抑制活性的抗肿瘤抗生素,对PP2A具有高度选择性。
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3
Structure-activity relationship studies of fostriecin, cytostatin, and key analogs, with PP1, PP2A, PP5, and( beta12-beta13)-chimeras (PP1/PP2A and PP5/PP2A), provide further insight into the inhibitory actions of fostriecin family inhibitors.福司曲星、细胞抑制素及关键类似物与PP1、PP2A、PP5以及(β12-β13)嵌合体(PP1/PP2A和PP5/PP2A)之间的构效关系研究,为深入了解福司曲星家族抑制剂的抑制作用提供了更多见解。
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Fostriecin: chemistry and biology.福司曲星:化学与生物学
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Importance of the beta12-beta13 loop in protein phosphatase-1 catalytic subunit for inhibition by toxins and mammalian protein inhibitors.蛋白磷酸酶-1催化亚基中β12-β13环在毒素和哺乳动物蛋白抑制剂抑制作用中的重要性。
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Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition.福司曲星不饱和内酯的基本作用及其对选择性蛋白磷酸酶抑制的影响。
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Purification and identification of a novel subunit of protein serine/threonine phosphatase 4.蛋白丝氨酸/苏氨酸磷酸酶4一种新亚基的纯化与鉴定
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Fostriecin-mediated G2-M-phase growth arrest correlates with abnormal centrosome replication, the formation of aberrant mitotic spindles, and the inhibition of serine/threonine protein phosphatase activity.福司曲星介导的G2-M期生长停滞与中心体复制异常、异常有丝分裂纺锤体的形成以及丝氨酸/苏氨酸蛋白磷酸酶活性的抑制相关。
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The predicted beta12-beta13 loop is important for inhibition of PP2Acalpha by the antitumor drug fostriecin.预测的β12-β13环对于抗肿瘤药物福司曲星抑制PP2Aα很重要。
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