Cell cycle regulatory functions of the human oncoprotein MDM2.
Cell cycle regulatory functions of the human oncoprotein MDM2.
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发表时间：
2003-12
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通讯作者：
S. Deb
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作者：
S. Deb
由小鼠双分钟 2 (mdm2) 基因或其人类同源物编码的蛋白质 (MDM2) 被称为癌蛋白。人类恶性肿瘤，特别是乳腺肿瘤和软组织肉瘤经常过度表达 MDM2。来自转化小鼠细胞系的 mdm2 基因的人工扩增增强了小鼠细胞的致瘤潜力。与其致瘤特性一致，小鼠或人类 MDM2 可以使肿瘤抑制因子 p53 的多种功能失活，并可以降解 p53。该蛋白还与其他肿瘤抑制因子相互作用，这些相互作用可能有助于其致瘤特性。尽管具有致癌作用，小鼠或人类 MDM2 仍可诱导正常人类或小鼠细胞中的 G(1) 阻滞。一些携带已知基因突变的细胞系对 MDM2 介导的生长停滞不敏感。本综述旨在收集有关可能调节细胞周期的 MDM2 功能的可用信息，并讨论如何将这些信息融入到一个模型中，该模型可以解释 MDM2 两种明显相反的 G(1) 阻滞和致癌功能。
The protein (MDM2) coded by the mouse double minute-2 (mdm2) gene or its human homologue is well known as an oncoprotein. Malignant human tumors particularly breast tumors and soft tissue sarcomas frequently overexpress MDM2. Artificial amplification of mdm2 gene derived from a transformed murine cell line enhances tumorigenic potential of murine cells. Consistent with its tumorigenic property, mouse or human MDM2 can inactivate several functions of the tumor suppressor p53 and can degrade p53. The protein also interacts with other tumor suppressors, and these interactions may contribute to its tumorigenic property. In spite of its oncogenic role, mouse or human MDM2 induces G(1) arrest in normal human or murine cells. Some cell lines bearing known genetic mutations are insensitive to MDM2-mediated growth arrest. This review is aimed to collect available information on the functions of MDM2 that could potentially regulate cell cycle and to discuss how this information may fit in one model that could explain the two apparently opposite G(1) arrest and oncogenic function of MDM2.