Janostiak Radoslav, Torres-Sanchez Ariadna, Posas Francesc, de Nadal Eulàlia
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Cancers (Basel). 2022 Feb 28;14(5):1265. doi: 10.3390/cancers14051265.
The retinoblastoma protein (Rb1) is a prototypical tumor suppressor protein whose role was described more than 40 years ago. Together with p107 (also known as RBL1) and p130 (also known as RBL2), the Rb1 belongs to a family of structurally and functionally similar proteins that inhibits cell cycle progression. Given the central role of Rb1 in regulating proliferation, its expression or function is altered in most types of cancer. One of the mechanisms underlying Rb-mediated cell cycle inhibition is the binding and repression of E2F transcription factors, and these processes are dependent on Rb1 phosphorylation status. However, recent work shows that Rb1 is a convergent point of many pathways and thus the regulation of its function through post-translational modifications is more complex than initially expected. Moreover, depending on the context, downstream signaling can be both E2F-dependent and -independent. This review seeks to summarize the most recent research on Rb1 function and regulation and discuss potential avenues for the design of novel cancer therapies.
视网膜母细胞瘤蛋白（Rb1）是一种典型的肿瘤抑制蛋白，其作用在40多年前就已被描述。Rb1与p107（也称为RBL1）和p130（也称为RBL2）一起，属于一类结构和功能相似的蛋白质家族，该家族可抑制细胞周期进程。鉴于Rb1在调节细胞增殖中的核心作用，其表达或功能在大多数癌症类型中都会发生改变。Rb介导的细胞周期抑制的潜在机制之一是E2F转录因子的结合和抑制，而这些过程取决于Rb1的磷酸化状态。然而，最近的研究表明，Rb1是许多信号通路的汇聚点，因此通过翻译后修饰对其功能的调节比最初预期的更为复杂。此外，根据具体情况，下游信号传导既可以是E2F依赖的，也可以是E2F非依赖的。本综述旨在总结关于Rb1功能和调节的最新研究，并讨论设计新型癌症治疗方法的潜在途径。
