RB1, development, and cancer.
RB1, development, and cancer.
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DOI：
10.1016/b978-0-12-380916-2.00005-x
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发表时间：
2011
影响因子：
--
通讯作者：
Goodrich, David W.
中科院分区：
文献类型：
--
作者：
Chinnam, Meenalakshmi;Goodrich, David W.
RB1基因是第一个发现的肿瘤抑制基因，其突变失活是导致人类癌症的原因，儿童癌症视网膜母细胞瘤。自发现以来的25年研究不仅阐明了RB1在人类癌症中的一般作用，而且还阐明了其在正常发育中的关键重要性。了解RB1编码蛋白pRb的分子功能是一个长期的目标，它有望为我们了解癌症，其与正常发育的关系以及对抗这种疾病的可能治疗策略提供信息。实现这一目标一直很困难，pRb和相关蛋白质的复杂性使其复杂化。这篇综述的目的是探讨这一假设，即在其核心，pRb的分子功能是动态调节的位置特异性组装或拆卸的蛋白质复合物的DNA响应于各种信号通路的输出。这些蛋白质复合物参与与DNA相关的多种分子过程，包括基因转录、DNA复制、DNA修复和有丝分裂。通过调节这些过程，RB1在正常发育和癌症中发挥着独特的重要作用。
The RB1 gene is the first tumor suppressor gene identified whose mutational inactivation is the cause of a human cancer, the pediatric cancer retinoblastoma. The twenty five years of research since its discovery has not only illuminated a general role for RB1 in human cancer, but also its critical importance in normal development. Understanding the molecular function of the RB1 encoded protein, pRb, is a long-standing goal that promises to inform our understanding of cancer, its relationship to normal development, and possible therapeutic strategies to combat this disease. Achieving this goal has been difficult, complicated by the complexity of pRb and related proteins. The goal of this review is to explore the hypothesis that, at its core, the molecular function of pRb is to dynamically regulate the location specific assembly or disassembly of protein complexes on the DNA in response to the output of various signaling pathways. These protein complexes participate in a variety of molecular processes relevant to DNA including gene transcription, DNA replication, DNA repair, and mitosis. Through regulation of these processes, RB1 plays a uniquely prominent role in normal development and cancer.