Mammalian mitotic centromere‐associated kinesin (MCAK)
Mammalian mitotic centromere‐associated kinesin (MCAK)
复制标题
哺乳动物有丝分裂着丝粒相关驱动蛋白 (MCAK)
DOI：
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
K. Sakaguchi
中科院分区：
文献类型：
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作者：
Satoko Aoki;K. Ohta;T. Yamazaki;F. Sugawara;K. Sakaguchi
磺基喹诺vovosylacylglycerols (SQAGs)，特别是在甘油部分含有C18脂肪酸的化合物，可能是临床上有前景的抗肿瘤和/或免疫抑制剂。它们最初被发现是哺乳动物DNA聚合酶的抑制剂。然而，SQAGs不仅可以在S期阻滞培养的哺乳动物细胞，也可以在M期阻滞培养的哺乳动物细胞，这表明它们具有多个分子靶点。利用T7噬菌体展示方法筛选候选靶分子，确定氨基酸序列。同源性研究表明，这是一种哺乳动物有丝分裂着丝粒相关激酶（MCAK），而不是DNA聚合酶。分析显示，与重组MCAK结合的SQAGs的KD值为3.1 × 10−4 ~ 6.2 × 10−5m。使用EGFP -全长MCAK融合构建的体内微管解聚实验表明，MCAK的微管解聚活性受到抑制。根据这些结果，我们得出结论，临床上有希望的SQAGs至少有两个不同的分子靶点，DNA聚合酶和MCAK。应该强调的是，MCAK抑制剂以前从未报道过，因此有很大的临床应用潜力。
Sulfoquinovosylacylglycerols (SQAGs), in particular compounds with C18 fatty acid(s) on the glycerol moiety, may be clinically promising antitumor and/or immunosuppressive agents. They were found originally as inhibitors of mammalian DNA polymerases. However, SQAGs can arrest cultured mammalian cells not only at S phase but also at M phase, suggesting they have several molecular targets. A screen for candidate target molecules using a T7 phage display method identified an amino acid sequence. An homology search showed this to be a mammalian mitotic centromere‐associated kinesin (MCAK), rather than a DNA polymerase. Analyses showed SQAGs bound to recombinant MCAK with a KD = 3.1 × 10−4 to 6.2 × 10−5m. An in vivo microtubule depolymerization assay, using EGFP‐full length MCAK fusion constructs, indicated inhibition of the microtubule depolymerization activity of MCAK. From these results, we conclude that clinically promising SQAGs have at least two different molecular targets, DNA polymerases and MCAK. It should be stressed that inhibitors of MCAK have never been reported previously so that there is a major potential for clinical utility.
影响因子：
16
作者：
Hunter, AW;Caplow, M;Howard, J
通讯作者：
Howard, J