It Takes 15 to Tango: Making Sense of the Many Ubiquitin Ligases of p53.
It Takes 15 to Tango: Making Sense of the Many Ubiquitin Ligases of p53.
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DOI：
10.1177/1947601912455198
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发表时间：
2012-03-01
期刊：
影响因子：
--
通讯作者：
Grossman, Steven R
中科院分区：
文献类型：
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作者：
Love, Ian M;Grossman, Steven R
转录因子P53调节许多细胞过程，以防止肿瘤的发生。细胞周期抑制、细胞凋亡和自噬都是由P53以一种特定于细胞和上下文的方式调节的，这强调了在大多数情况下保持低P53活性的必要性。P53主要通过其调节的泛素化和许多不同因素的降解而受到控制，这些因素的作用可能反映了抑制P53活性的复杂的特定背景需要。在这些E3泛素连接酶中，最主要的是普遍表达的原癌基因MDM2，它的缺失使脊椎动物无法限制P53的活性，导致早期胚胎死亡。到目前为止，MDM2已被证实是许多组织和生物体中P53的关键的、通用的E3泛素连接酶，但也发现了其他E3连接酶对P53活性的影响尚不清楚。在这篇综述中，我们总结了关于p53活性是如何受MDM2以外的多种泛素连接酶控制的最新进展。
The transcription factor p53 regulates numerous cellular processes to guard against tumorigenesis. Cell-cycle inhibition, apoptosis, and autophagy are all regulated by p53 in a cell- and context-specific manner, underscoring the need for p53 activity to be kept low in most circumstances. p53 is kept in check primarily through its regulated ubiquitination and degradation by a number of different factors, whose contributions may reflect complex context-specific needs to restrain p53 activity. Chief among these E3 ubiquitin ligases in p53 homeostasis is the ubiquitously expressed proto-oncogene MDM2, whose loss renders vertebrates unable to limit p53 activity, resulting in early embryonic lethality. MDM2 has been validated as a critical, universal E3 ubiquitin ligase for p53 in numerous tissues and organisms to date, but additional E3 ligases have also been identified for p53 whose contribution to p53 activity is unclear. In this review, we summarize the recent advances in our knowledge regarding how p53 activity is apparently controlled by a multitude of ubiquitin ligases beyond MDM2.