HGNC Approved Gene Symbol: RPS6
Cytogenetic location: 9p22.1 Genomic coordinates (GRCh38): 9:19,375,715-19,380,236 (from NCBI)
Ribosomal protein S6 is the major substrate of protein kinases (e.g., 300075) in eukaryotic ribosomes. Heinze et al. (1988) used polyclonal antibodies directed against a synthetic octopeptide of the phosphorylation site of the ribosomal protein S6 of rat liver to screen a lambda-gt11 cDNA expression library of human lymphoblasts. In this way an S6-specific clone was isolated. It consisted of the complete coding sequence of 747 bases. The sequence of 249 amino acids deduced from the nucleotide sequence showed a high degree of similarity to that of rat liver S6. Southern blot analysis of human genomic DNA suggested that multiple genes exist for the S6 protein. Independently, Lott and Mackie (1988) cloned human RPS6 cDNAs using oligonucleotides based on the rat Rps6 and yeast Rps10 amino acid sequences.
By Northern blot analysis using a rat Rps6 probe, Pogue-Geile et al. (1991) found increased levels of RPS6 mRNA in 3 of 3 human colorectal tumors and 2 of 4 human colon polyps relative to matched normal colonic mucosa. RPS6 is expressed as an approximately 820-bp transcript.
Antoine and Fried (1992) demonstrated that the RPS6 gene is 3,979 bp long and comprises 6 exons.
Using a PCR product for the analysis of rodent/human somatic cell hybrids, Feo et al. (1992) mapped the RPS6 gene to 9pter-p13. By fluorescence in situ hybridization, Antoine and Fried (1992) sublocalized the RPS6 gene to 9p21. Kenmochi et al. (1998) confirmed the mapping assignment reported by Antoine and Fried (1992).
Because ribosome biogenesis plays an essential role in cell proliferation, control mechanisms may have evolved to recognize lesions in this critical anabolic process. To test this possibility, Volarevic et al. (2000) conditionally deleted the gene encoding 40S ribosomal protein S6 in the liver of adult mice. Unexpectedly, livers from fasted animals deficient in S6 grew in response to nutrients even though biogenesis of 40S ribosomes was abolished. However, liver cells failed to proliferate or induce cyclin E expression after partial hepatectomy, despite formation of active cyclin D-CDK4 complexes. Volarevic et al. (2000) concluded that their results implied that abrogation of 40S ribosome biogenesis may induce a checkpoint control that prevents cell cycle progression.
In order to study the relationship between ribosome biogenesis, cell growth, and proliferation, Sulic et al. (2005) conditionally deleted 1 or 2 alleles of Rps6 in mouse thymi. Complete Rps6 deletion abrogated T-cell development. Hemizygous Rps6 expression had no effect on T-cell maturation in the thymus but inhibited the accumulation of T cells in the spleen and lymph nodes as a result of their decreased survival in peripheral lymphoid organs. Stimulation of Rps6-heterozygous T cells induced a normal increase in size, but cell cycle progression was impaired in a p53 (TP53; 191170)-dependent manner.
Antoine, M., Fried, M. The organization of the intron-containing human S6 ribosomal protein (rpS6) gene and determination of its location at chromosome 9p21. Hum. Molec. Genet. 1: 565-570, 1992. [PubMed: 1301164] [Full Text: https://doi.org/10.1093/hmg/1.8.565]
Feo, S., Davies, B., Fried, M. The mapping of seven intron-containing ribosomal protein genes shows they are unlinked in the human genome. Genomics 13: 201-207, 1992. [PubMed: 1577483] [Full Text: https://doi.org/10.1016/0888-7543(92)90221-d]
Heinze, H., Arnold, H. H., Fischer, D., Kruppa, J. The primary structure of the human ribosomal protein S6 derived from a cloned cDNA. J. Biol. Chem. 263: 4139-4144, 1988. [PubMed: 3279029]
Kenmochi, N., Kawaguchi, T., Rozen, S., Davis, E., Goodman, N., Hudson, T. J., Tanaka, T., Page, D. C. A map of 75 human ribosomal protein genes. Genome Res. 8: 509-523, 1998. [PubMed: 9582194] [Full Text: https://doi.org/10.1101/gr.8.5.509]
Lott, J. B., Mackie, G. A. Isolation and characterization of cloned cDNAs that code for human ribosomal protein S6. Gene 65: 31-39, 1988. [PubMed: 2840355] [Full Text: https://doi.org/10.1016/0378-1119(88)90414-3]
Pogue-Geile, K., Geiser, J. R., Shu, M., Miller, C., Wool, I. G., Meisler, A. I., Pipas, J. M. Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein. Molec. Cell. Biol. 11: 3842-3849, 1991. [PubMed: 1712897] [Full Text: https://doi.org/10.1128/mcb.11.8.3842-3849.1991]
Sulic, S., Panic, L., Barkic, M., Mercep, M., Uzelac, M., Volarevic, S. Inactivation of S6 ribosomal protein gene in T lymphocytes activates a p53-dependent checkpoint response. Genes Dev. 19: 3070-3082, 2005. [PubMed: 16357222] [Full Text: https://doi.org/10.1101/gad.359305]
Volarevic, S., Stewart, M. J., Ledermann, B., Zilberman, F., Terracciano, L., Montini, E., Grompe, M., Kozma, S. C., Thomas, G. Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6. Science 288: 2045-2047, 2000. [PubMed: 10856218] [Full Text: https://doi.org/10.1126/science.288.5473.2045]