Berto Giovanna, Ferreira-Cerca Sébastien, De Wulf Peter
Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123, Povo, TN, Italy.
Biochemistry III-Institute for Biochemistry, Genetics and Microbiology, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
Curr Genet. 2019 Apr;65(2):457-466. doi: 10.1007/s00294-018-0912-y. Epub 2018 Dec 4.
The atypical Rio1 protein kinases/ATPases, which exist in most archaea and eukaryotes, have been studied intensely to understand how they promote small ribosomal subunit (SSU) maturation. However, mutant and knockdown phenotypes in various organisms suggested roles in activities beyond SSU biogenesis, including the regulation of cell cycle progression (DNA transcription, replication, condensation, and segregation), cell division, metabolism, physiology, and development. Recent work with budding yeast, indeed, revealed that Rio1 (RIOK1 in metazoans) manages a large signaling network at the protein and gene levels via which it stimulates or restricts growth and division in response to nutrient availability. We examine how these findings translate to human cells and suggest that RIOK1 over-expression or mutations, as observed in primary cancer cells, may cause a mis-regulation of its network, contributing to cancer initiation and progression. We also reflect on how targeting RIOK1 might eradicate hitherto incurable tumors in the clinic.
非典型Rio1蛋白激酶/ATP酶存在于大多数古细菌和真核生物中，人们对其进行了深入研究，以了解它们如何促进小核糖体亚基（SSU）成熟。然而，各种生物体中的突变体和敲低表型表明，它们在SSU生物合成之外的活动中发挥作用，包括细胞周期进程（DNA转录、复制、凝聚和分离）、细胞分裂、代谢、生理和发育的调控。事实上，最近对芽殖酵母的研究表明，Rio1（后生动物中的RIOK1）在蛋白质和基因水平上管理着一个庞大的信号网络，通过该网络，它根据营养物质的可用性刺激或限制生长和分裂。我们研究了这些发现如何转化到人类细胞中，并表明在原发性癌细胞中观察到的RIOK1过表达或突变可能导致其网络的失调，从而促进癌症的发生和发展。我们还思考了靶向RIOK1如何在临床上根除迄今无法治愈的肿瘤。
