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一种功能——多种机制:p53作为转录抑制因子的多种活性

One function--multiple mechanisms: the manifold activities of p53 as a transcriptional repressor.

作者信息

Böhlig Levin, Rother Karen

机构信息

Molecular Oncology, Department of Obstetrics and Gynecology, University of Leipzig, Leipzig, Germany.

出版信息

J Biomed Biotechnol. 2011;2011:464916. doi: 10.1155/2011/464916. Epub 2011 Mar 8.

Abstract

Maintenance of genome integrity is a dynamic process involving complex regulation systems. Defects in one or more of these pathways could result in cancer. The most important tumor-suppressor is the transcription factor p53, and its functional inactivation is frequently observed in many tumor types. The tumor suppressive function of p53 is mainly attributed to its ability to regulate numerous target genes at the transcriptional level. While the mechanism of transcriptional induction by p53 is well characterized, p53-dependent repression is not understood in detail. Here, we review the manifold mechanisms of p53 as a transcriptional repressor. We classify two different categories of repressed genes based on the underlying mechanism, and novel mechanisms which involve regulation through noncoding RNAs are discussed. The complete elucidation of p53 functions is important for our understanding of its tumor-suppressor activity and, therefore, represents the key for the development of novel therapeutic approaches.

摘要

基因组完整性的维持是一个涉及复杂调控系统的动态过程。这些途径中一个或多个出现缺陷可能导致癌症。最重要的肿瘤抑制因子是转录因子p53,其功能失活在许多肿瘤类型中经常可见。p53的肿瘤抑制功能主要归因于其在转录水平调控众多靶基因的能力。虽然p53转录诱导的机制已得到充分表征,但p53依赖的抑制作用尚未得到详细了解。在这里,我们综述了p53作为转录抑制因子的多种机制。我们根据潜在机制对两类不同的受抑制基因进行了分类,并讨论了涉及通过非编码RNA进行调控的新机制。对p53功能的全面阐明对于我们理解其肿瘤抑制活性很重要,因此是开发新治疗方法的关键。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cafc/3062963/90d9aecd753b/JBB2011-464916.001.jpg

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