Functional and physical communication between oncoproteins and tumor suppressors.
Functional and physical communication between oncoproteins and tumor suppressors.
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癌蛋白和肿瘤抑制因子之间的功能和物理通讯。
DOI：
10.1007/s00018-005-5199-8
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Prochownik,EV
中科院分区：
文献类型：
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作者：
Prochownik,EV
癌基因（c-onc's）和肿瘤抑制基因（TS's）的发现导致了癌症是由这些基因或其产物中的每一类缺陷引起的概念。最近，已经认识到c-onc和TS蛋白经常影响彼此的功能。在此背景下，我回顾了两个经典的TS，p53和视网膜母细胞瘤蛋白，以及它们失活的后果。各种形式的基因组不稳定性（GI）的转化细胞的高突变率的基础进行了讨论。特别强调的是放在概念上，GI不仅是一个不可分割的一部分，转换状态，但是一个先决条件。增加的氧化DNA损伤，和/或无法修复它，可导致GI。然后，该综述讨论了最近的观察结果表明，TS蛋白peroxiredoxin 1（prdx 1）的丢失和c-onc蛋白c-Myc的表达增加，各自导致氧化性DNA损伤增加。c-onc-TS相互作用的关键性质是由prdx 1和c-Myc之间发生的相互作用所强调的，前者蛋白质调节后者产生的DNA损伤活性氧。这些蛋白质和其他蛋白质之间的密切联系是c-onc和TS必须保持的微妙平衡行为的范例，以便正确控制正常的DNA复制和细胞增殖，同时最大限度地减少潜在的肿瘤突变的获得。
The discovery of oncogenes (c-onc’s) and tumor suppressors (TS’s) has led to the concept that cancer arises from defects in each of these classes of genes or their products. More recently, it has been appreciated that c-onc and TS proteins often affect one another’s functions. Within this context, I review the two classical TS’s, p53 and the retinoblastoma protein, and the consequences of their inactivation. The various forms of genomic instability (GI) that underly the high mutation rates of transformed cells are then discussed. Particular emphasis is placed upon the concept that GI is not only an integral part of the transformed state but is a prerequisite. Increased oxidative DNA damage, and/or an inabiliy to repair it, can lead to GI. The review then discusses recent observations showing that loss of the TS protein peroxiredoxin 1 (prdx1) and increased expression of the c-onc protein c-Myc, each leads to increased oxidative DNA damage. The critical nature of the c-onc-TS interaction is underscored by that occurring between prdx1 and c-Myc, with the former protein regulating the production of DNA-damaging reactive oxygen species by the latter. The intimate association between these proteins and others serves as a paradigm for the exquisite balancing act that c-onc’s and TS’s must maintain in order to properly control normal DNA replication and cellular proliferation while simultaneously minimizing the acquisition of potentially neoplastic mutations.