p53/MDM2 Research Group, School of Cancer Studies, University of Liverpool, L69 3GA, UK.
FEBS Lett. 2010 Nov 19;584(22):4695-702. doi: 10.1016/j.febslet.2010.10.049. Epub 2010 Oct 29.
Recent studies connect MDM2 with increased cell motility, invasion and/or metastasis proposing an MDM2-mediated ubiquitylation-dependent mechanism. Interestingly, in renal cell carcinoma (RCC) p53/MDM2 co-expression is associated with reduced survival which is independently linked with metastasis. We therefore investigated whether expression of p53 and/or MDM2 promotes aggressive cell phenotypes. Our data demonstrate that MDM2 promotes increased motility and invasiveness in RCC cells (N.B. similar results are obtained in non-RCC cells). This study shows for the first time both that endogenous MDM2 significantly contributes to cell motility and that this does not depend upon the MDM2 RING-finger, i.e. is independent of ubiquitylation (and NEDDylation). Our data suggest that protein-protein interactions provide a likely mechanistic basis for MDM2-promoted motility which may constitute future therapeutic targets.
最近的研究将 MDM2 与增加的细胞迁移、侵袭和/或转移联系起来，提出了一种 MDM2 介导的泛素化依赖性机制。有趣的是，在肾细胞癌 (RCC) 中，p53/MDM2 共表达与降低的存活率相关，而存活率与转移独立相关。因此，我们研究了 p53 和/或 MDM2 的表达是否促进侵袭性细胞表型。我们的数据表明，MDM2 促进 RCC 细胞的迁移和侵袭能力增加（注：在非 RCC 细胞中也获得了类似的结果）。这项研究首次表明，内源性 MDM2 显著促进细胞迁移，并且这并不依赖于 MDM2 的 RING 指，即独立于泛素化（和 NEDDylation）。我们的数据表明，蛋白质-蛋白质相互作用为 MDM2 促进迁移提供了一个可能的机制基础，这可能成为未来的治疗靶点。
