The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1
The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1
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DOI：
10.1093/nar/gkf678
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发表时间：
2002-12-15
影响因子：
14.9
通讯作者：
Hannon, GJ
中科院分区：
文献类型：
--
作者：
Du, J;Hannon, GJ
中心体激酶 Aurora-A/STK15 活性的改变与中心体扩增、基因组不稳定和细胞转化有关。 STK15 如何参与所有这些过程在很大程度上仍然是个谜。 STK15 的活性受磷酸化和泛素介导的降解调节，并与蛋白磷酸酶 1 (PP1) 和 CDC20 发生物理相互作用。然而，这些修饰和相互作用的确切作用尚未得到充分认识。在这里，我们表明 STK15 与假定的肿瘤和转移抑制因子 NM23-H1 相关。最初在双杂交测定中发现 STK15 和 NM23 在酵母中相互作用。通过细胞裂解物的免疫共沉淀和生化分级分离证实了人类细胞中这些蛋白质的关联，表明 STK15 和 NM23-H1 存在于稳定的物理复合物中。值得注意的是，无论正常人成纤维细胞中微管网络的完整性如何，SKT15 和 NM23 在整个细胞周期中都定位于中心体。
Alterations in the activity of the centrosomal kinase, Aurora-A/STK15, have been implicated in centrosome amplification, genome instability and cellular transformation. How STK15 participates in all of these processes remains largely mysterious. The activity of STK15 is regulated by phosphorylation and ubiquitin-mediated degradation, and physically interacts with protein phosphatase 1 (PP1) and CDC20. However, the precise roles of these modifications and interactions have yet to be fully appreciated. Here we show that STK15 associates with a putative tumor and metastasis suppressor, NM23-H1. STK15 and NM23 were initially found to interact in yeast in a two-hybrid assay. Association of these proteins in human cells was confirmed by co-immunoprecipitation from cell lysates and biochemical fractionation indicating that STK15 and NM23-H1 are present in a stable, physical complex. Notably, SKT15 and NM23 both localize to centrosomes throughout the cell cycle irrespective of the integrity of the microtubule network in normal human fibroblasts.