突变型 p53 相互作用组鉴定出脑啡肽酶为 p53R273H 特异性结合伴侣，促进侵袭。
Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding partner that promotes invasion.
机构信息
Quantitative Proteomics Group, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
出版信息
EMBO Rep. 2012 Jun 29;13(7):638-44. doi: 10.1038/embor.2012.74.
Abstract
The invasiveness of tumour cells depends on changes in cell shape, polarity and migration. Mutant p53 induces enhanced tumour metastasis in mice, and human cells overexpressing p53R273H have aberrant polarity and increased invasiveness, demonstrating the 'gain of function' of mutant p53 in carcinogenesis. We hypothesize that p53R273H interacts with mutant p53-specific binding partners that control polarity, migration or invasion. Here we analyze the p53R273H interactome using stable isotope labelling by amino acids in cell culture and quantitative mass spectrometry, and identify at least 15 new potential mutant p53-specific binding partners. The interaction of p53R273H with one of them--nardilysin (NRD1)--promotes an invasive response to heparin binding-epidermal growth factor-like growth factor that is p53R273H-dependant but does not require Rab coupling protein or p63. Advanced proteomics has thus allowed the detection of a new mechanism of p53-driven invasion.
摘要
肿瘤细胞的侵袭性取决于细胞形态、极性和迁移的变化。突变型 p53 可诱导小鼠肿瘤转移增强，过表达 p53R273H 的人类细胞表现出异常的极性和侵袭性增加，表明突变型 p53 在致癌作用中具有“功能获得”。我们假设 p53R273H 与控制极性、迁移或侵袭的突变型 p53 特异性结合伙伴相互作用。在这里，我们使用细胞培养中的稳定同位素标记氨基酸和定量质谱分析了 p53R273H 的相互作用组，鉴定了至少 15 个新的潜在突变型 p53 特异性结合伙伴。p53R273H 与其中之一——nardilysin（NRD1）的相互作用促进了肝素结合-表皮生长因子样生长因子的侵袭反应，这种反应依赖于 p53R273H，但不需要 Rab 偶联蛋白或 p63。先进的蛋白质组学因此允许检测到一种新的 p53 驱动的侵袭机制。
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