LIM-kinase 2, a regulator of actin dynamics, is involved in mitotic spindle integrity and sensitivity to microtubule-destabilizing drugs.
作者： S T Po'uha , M S Y Shum , A Goebel , O Bernard , M Kavallaris
DOI: 10.1038/ONC.2009.367
关键词:
摘要: LIM-kinase 2 (LIMK2) belongs to the LIMK family of proteins, which comprises LIMK1 and LIMK2. Both proteins regulate actin polymerization through phosphorylation inactivation depolymerizing factor cofilin. In this study, we show that level LIMK2 protein is increased in neuroblastoma, BE(2)-C cells, selected for resistance microtubule-destabilizing agents, vincristine colchicine. However, phosphorylated was similar resistant parental cells. contrast, phospho-cofilin greatly drug-resistant Downregulation expression increases sensitivity neuroblastoma SH-EP cells vinblastine but not microtubule-stabilizing while it's overexpression its vincristine. Its vincristine-induced mitotic arrest moderately inhibited knockdown suggesting drug an alternative mechanism other then apoptosis. Moreover, downregulation induces formation abnormal spindles, effect enhanced presence agents. important normal spindle altered mediates microtubule destabilizing These findings suggest inhibition activity may be used treatment tumors drugs.
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