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长春新碱调节乳腺癌细胞中抗凋亡蛋白HSP27的磷酸化。

Vincristine regulates the phosphorylation of the antiapoptotic protein HSP27 in breast cancer cells.

作者信息

Casado Pedro, Zuazua-Villar Pedro, del Valle Eva, Martínez-Campa Carlos, Lazo Pedro S, Ramos Sofía

机构信息

Departamento de Bioquimica y Biología Molecular, Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33071 Oviedo, Spain.

出版信息

Cancer Lett. 2007 Mar 18;247(2):273-82. doi: 10.1016/j.canlet.2006.05.005. Epub 2006 Jul 14.

Abstract

Vincristine is an antitumor drug that inhibits microtubule polymerization, causes G2/M arrest and induces apoptosis. 2D-PAGE and MALDI-TOF-MS analysis of vincristine effects on MCF7 cells, revealed a vincristine upregulated form and a vincristine downregulated form of the antiapoptotic protein HSP27. These findings linked to the lack of vincristine effect over HSP27 mRNA, suggest a protein post-translational modification. Further assays indicated the presence of a phosphorylated peptide, containing serine 82, only in the vincristine upregulated form. Serine 82 phosphorylation was confirmed using specific antibodies. Thus, phosphorylation of HSP27 may play a role in the cellular response to vincristine.

摘要

长春新碱是一种抗肿瘤药物,它能抑制微管聚合,导致G2/M期阻滞并诱导细胞凋亡。对长春新碱作用于MCF7细胞的二维聚丙烯酰胺凝胶电泳(2D-PAGE)和基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)分析显示,抗凋亡蛋白HSP27存在长春新碱上调型和长春新碱下调型。这些与长春新碱对HSP27 mRNA缺乏作用相关的发现提示存在蛋白质翻译后修饰。进一步检测表明,仅在长春新碱上调型中存在一个含丝氨酸82的磷酸化肽段。使用特异性抗体证实了丝氨酸82的磷酸化。因此,HSP27的磷酸化可能在细胞对长春新碱的反应中发挥作用。

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