Molecular pathways: regulation and targeting of kinetochore-microtubule attachment in cancer.
Molecular pathways: regulation and targeting of kinetochore-microtubule attachment in cancer.
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DOI：
10.1158/1078-0432.ccr-13-0645
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发表时间：
2015-01-15
期刊：
影响因子：
--
通讯作者：
Paddison PJ
中科院分区：
文献类型：
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作者：
Herman JA;Toledo CM;Olson JM;DeLuca JG;Paddison PJ
动点是在有丝分裂过程中组装在着丝粒DNA上的大型蛋白质结构，它与有丝分裂纺锤体的微管结合，协调和推动染色体的运动。动粒-微管(KT-MT)连接的去调控与染色体不稳定和癌症进化有关；然而，癌细胞中KT-MT连接缺陷的性质和来源仍很大程度上未知。在这里，我们重点介绍了最近的发现，即癌基因驱动的动粒调节变化发生在多形性胶质母细胞瘤(GBM)和可能表现出染色体不稳定的其他癌症中，这带来了新的治疗机会。特别是，我们认为BubR1的GLE2p结合序列(GLEBS)结构域和新发现的两个动粒相关蛋白BuGZ是GBM的候选治疗靶点。
Kinetochores are large protein structures assembled on centromeric DNA during mitosis that bind to microtubules of the mitotic spindle to orchestrate and power chromosome movements. Deregulation of kinetochore-microtubule (KT-MT) attachments has been implicated in driving chromosome instability and cancer evolution; however, the nature and source of KT-MT attachment defects in cancer cells remain largely unknown. Here we highlight recent findings suggesting that oncogene-driven changes in kinetochore regulation occur in Glioblastoma multiforme (GBM) and possibly other cancers exhibiting chromosome instability, giving rise to novel therapeutic opportunities. In particular, we consider the GLE2p-binding sequence (GLEBS) domains of BubR1 and the newly discovered BuGZ, two kinetochore associated proteins, as candidate therapeutic targets for GBM.