Splice variants of MDM2 in oncogenesis.
Splice variants of MDM2 in oncogenesis.
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DOI：
10.1007/978-94-017-9211-0_14
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Bargonetti, Jill
中科院分区：
文献类型：
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作者：
Rosso, Melissa;Okoro, Danielle E;Bargonetti, Jill
许多类型的人类癌症过度表达MDM2蛋白。这些癌症的一个共同特征是mdm2剪接变异体的相关增加。这里提供了一个综合列表，基于文献综述，超过70个mdm2变体。这些变异根据框架内与框架外的状态及其翻译成异构体蛋白的潜力（或能力）进行分组。我们描述了这些mdm2剪接变异mrna的假定功能，以及与mdm2转录和剪接增加相关的机制驱动因素。最常研究的变异体mdm2-a、-b和-c的矛盾信号转导功能在存在和不存在野生型p53的情况下得到解决。这些结果从肿瘤促进到生长抑制各不相同。最后，我们提出了内源性MDM2蛋白检测的问题，以及通常用于检测MDM2的抗体中有多少不能全面反映同种异构体蛋白的细胞表征。这篇综述为有兴趣了解mdm2 mrna及其蛋白异构体的复杂性以及mdm2异构体在癌症进展中可能发挥的作用的个人提供了一个焦点。
Many types of human cancers overexpress MDM2 protein. A common characteristic among these cancers is an associated increase in mdm2 splice variants. Provided here is a comprehensive list, based on a literature review, of over 70 mdm2 variants. These variants are grouped according to in-frame versus out-of-frame status and their potential (or ability) to be translated into isoform proteins. We describe the putative functions for these mdm2 splice variant mRNAs, as well as the mechanistic drivers associated with increased mdm2 transcription and splicing. The paradoxical signal transduction functions of the most commonly studied variants mdm2-a,-b and -c are addressed for their outcomes in the presence and absence of wild-type p53. These outcomes vary from tumor promotion to growth arrest. Finally, we present issues in the detection of endogenous MDM2 protein and how many of the antibodies commonly used to detect MDM2 do not present a full picture of the cellular representation of the isoform proteins. This review provides a focusing lens for individuals interested in learning about the complexities of mdm2 mRNAs and their protein isoforms as well as the roles MDM2 isoforms may play in cancer progression.