The Rio1 protein kinases/ATPases: conserved regulators of growth, division, and genomic stability

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.