文章：

视网膜母细胞瘤肿瘤抑制因子在发展和癌症

The retinoblastoma tumour suppressor in development and cancer

原文发布日期：2002-12-01

DOI: 10.1038/nrc950

类型: Review Article

开放获取: 否

要点：

1. The retinoblastoma gene (RB) was the first tumour suppressor to be cloned, but the mechanism behind its role in tumour suppression remains unclear.
2. The retinoblastoma protein (RB) has been implicated in many cellular processes, such as regulation of the cell cycle, DNA-damage responses, DNA repair, DNA replication, protection against apoptosis, and differentiation, all of which could contribute to its function as a tumour suppressor.
3. RB is closely related to two genes in mice and humans (p107 and 130, which are not commonly mutated in tumours), which have been found to have partially redundant as well as opposing functions in genetic experiments in mice. Future studies are required to identify the similarities and differences between these proteins, which might explain the seemingly unique role of RB as a tumour suppressor.
4. As retinoblastomas do not arise as a consequence of Rb loss in mice, this model system is not ideal for studying this disease. However, this model system has provided information regarding the role of RB, p107 and p130 in development and tumorigenesis. Further experiments with conditional knockouts, as well as inter-crossing experiments, will provide a better insight into their roles in biological processes.
5. Biochemical experiments have provided information regarding the nature of various protein interactions with RB. Considering that there are more than 100 reported RB-binding proteins, much detailed structure/function mapping is required to clarify the biological relevance of all these interactions.
6. RB has also been associated with tumour growth, based on studies in which a constitutively active Rb allele gives rise to dysplasia in transgenic mice.

要点翻译：

1. 视网膜母细胞瘤基因（RB）是首个被克隆的肿瘤抑制基因，但其在肿瘤抑制中的作用机制仍不明确。
2. 视网膜母细胞瘤蛋白（RB）参与多种细胞过程，如细胞周期调控、DNA损伤应答、DNA修复、DNA复制、抗凋亡保护以及分化，这些功能可能共同贡献其肿瘤抑制特性。
3. RB与小鼠和人类中的两个基因（p107和p130，这两个基因在肿瘤中通常不发生突变）密切相关。小鼠遗传实验发现它们既存在功能冗余又具有相互拮抗的作用。未来需进一步研究这些蛋白的异同点，这可能解释RB作为肿瘤抑制因子的独特地位。
4. 由于小鼠视网膜母细胞瘤并非由Rb缺失直接引发，该模型系统并非研究此疾病的理想选择。但该模型仍为了解RB、p107和p130在发育和肿瘤发生中的作用提供了线索。通过条件性基因敲除和杂交实验等进一步研究，将更深入揭示它们在生物过程中的功能。
5. 生化实验已揭示了RB与多种蛋白质相互作用的性质。鉴于目前已报道的RB结合蛋白超过100种，需通过更精细的结构/功能定位分析来阐明这些相互作用的生物学意义。
6. 基于转基因小鼠中持续活性Rb等位基因导致发育异常的研究，RB也被认为与肿瘤生长相关。

英文摘要：

Since its discovery, the retinoblastoma (RB) tumour-suppressor protein has been a focal point of cancer research. Accumulating evidence indicates a complex role for RB in cell proliferation, differentiation and survival. To further complicate matters, proteins that are related to RB have redundant as well as antagonistic functions. Recent studies of knockout mice and cells that lack one or more of these proteins have begun to clarify their various context-specific functions and the unique activity of this tumour suppressor.

摘要翻译： 

自发现以来，视网膜母细胞瘤（RB）抑癌蛋白一直是癌症研究的焦点。越来越多的证据表明，RB在细胞增殖、分化和存活中发挥着复杂作用。更复杂的是，与RB相关的蛋白质既有冗余功能，也有拮抗功能。最近对敲除小鼠和缺乏一种或多种此类蛋白质的细胞的研究，开始阐明了它们在不同情境下的特定功能以及这一抑癌蛋白的独特活性。

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