Girolline, an antitumor compound isolated from a sponge, induces G2/M cell cycle arrest and accumulation of polyubiquitinated p53
Girolline, an antitumor compound isolated from a sponge, induces G2/M cell cycle arrest and accumulation of polyubiquitinated p53
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DOI：
10.1248/bpb.27.699
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发表时间：
2004-05-01
影响因子：
2
通讯作者：
Yokosawa, H
中科院分区：
文献类型：
--
作者：
Tsukamoto, S;Yamashita, K;Yokosawa, H
吉罗林是一种从海绵中分离出来的抗肿瘤化合物，据报道，它可以抑制体内蛋白质合成的终止步骤。在本研究中，我们发现吉洛林在几种肿瘤细胞系中诱导G2/M细胞周期阻滞。免疫化学分析显示，多泛素化的p53在吉洛林处理的细胞中积累，而其他多泛素化的细胞蛋白没有积累，表明吉洛林对p53的作用是特异性的。另一方面，吉洛林在体外没有抑制蛋白酶体的活性，在leptomycin B（一种核输出抑制剂）存在的情况下，几乎没有检测到多泛素化p53的积累。基于上述发现，我们提出吉洛林影响多泛素化p53向蛋白酶体募集的步骤。
Girolline, an antitumor compound isolated from a sponge, has been reported to inhibit the termination step of protein synthesis in vivo. In this study, we found that girolline induced G2/M cell cycle arrest in several tumor cell lines. Immunochemical analysis revealed that polyubiquitinated p53 was accumulated in girolline-treated cells, while other polyubiquitinated cellular proteins were not accumulated, indicating that the effect of girolline is specific for p53. On the other hand, girolline did not inhibit proteasome activity in vitro, and accumulation of polyubiquitinated p53 was scarcely detected in the presence of leptomycin B, an inhibitor of nuclear export. Based on the above findings, we propose that girolline affects the step of recruitment of polyubiquitinated p53 to the proteasome.