A study published in PlosOne by the Molecular Pathology and Oncology group of the VHIR, directed by Dr. Matilde Lleonart, has revealed a crucial —and unexpected— role of a ribosomal protein, called P1, in the "http://www.ncbi.nlm.nih.gov/pubmed/24959908" embryonic development of the nervous system.The project started 8 years ago, when the group led by Dr. Lleonart was seeking genes that could induce proliferation. They identified the "http://www.ncbi.nlm.nih.gov/pubmed/19233166" P1 protein whose expression turned out to be increased in "http://www.ncbi.nlm.nih.gov/pubmed/21040949" human tumors. In this study, performed in collaboration with researchers from the Leibniz Institute for Age Research, Jena, Germany, the authors wanted to understand the relevance of P1 in vivo. In other words, what happens when the protein is absent? They found that mice completely deficient for the protein (because both P1 alleles were inactivated) died before birth, while mice with one inactivated allele survived after birth but presented many defects such as reduced size, brain atrophty, an arrest in cell proliferation and an increase in cell death.The ribosome is a complex cellular factory where all new proteins are formed. Thus, defects in ribosomal proteins should lead to defects in protein synthesis. However, explains Dr. Lleonart, “the most surprising thing is that we did not find a defect in protein synthesis” Rather, P1 deficiency led to an increase in stress proteins that in turn results from an accumulation of mis-folded proteins. “This suggests that the protein has an extra-ribosomal function associated to protein folding” says Dr. Lleonart. Another unexpected result, according to the investigator, is that P1 disturbance particularly affects proliferating cells, very likely as a strategy to detect cellular stress and ensure their integrity as stem cells. “The role of the protein may depend on the tissue” concludes Dr. Lleonart, “since its deficiency does not affect non-embryonic cells such as spleen cells”.The authors point out that these results may have clinical implications in malignant cell proliferation. Dr. Lleonart’s group is now seeking to inhibit expression of P1 in tumor cells. Interestingly, the anti-proliferative effect of certain hormone-based treatments involves the downregulation of P1, suggesting that targeting these proteins in cancer may have potential clinical relevance.