Cell stemness is maintained upon concurrent expression of RB and the mitochondrial ribosomal protein S18-2
Muhammad Mushtaq, Larysa Kovalevska, Suhas Darekar, Alexandra Abramsson, Henrik Zetterberg, В. И. Кашуба, George Klein, Marie Arsenian‐Henriksson, Elena Kashuba
Abstract
Significance We here describe the essential roles of RB and MRPS18-2 (S18-2) in homeostasis of cell stemness. Mouse primary cells expressing both S18-2 and RB (designated as RH18RB) exhibited a stem cell phenotype. As a proof of principle, we demonstrated decreased expression of stem-cell–related genes in human mesenchymal stem cells upon down-regulation of S18-2 and RB. Notably, loss of the S18-2 protein resulted in embryonic lethality in zebrafish. To reveal putative molecular mechanisms, we demonstrated that S18-2, in a multimeric complex with RB, enhanced the E3-ubiquitin ligase activity of RNF2 toward histone H2A. Finally, based on our observation that RH18RB cells generated tumors in severe combined immunodeficiency mice, S18-2 could be a promising target in the development of cancer therapies.