Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, USA.
Curr Top Dev Biol. 2011;94:129-69. doi: 10.1016/B978-0-12-380916-2.00005-X.
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 25 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.
RB1 基因是首个被鉴定的肿瘤抑制基因，其突变失活是导致儿童癌症视网膜母细胞瘤的原因。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，也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目标，有望使我们深入了解癌症、癌症与正常发育的关系，以及对抗这种疾病的可能治疗策略。实现这一目标一直很困难，pRb 及其相关蛋白的复杂性使其变得更加复杂。本综述的目的是探讨这样一个假设，即在其核心，pRb 的分子功能是动态调节 DNA 上蛋白复合物的位置特异性组装或拆卸，以响应各种信号通路的输出。这些蛋白复合物参与与 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。通过对这些过程的调节，RB1 在正常发育和癌症中发挥着独特的重要作用。
