Loss of Ribosomal Protein L11 Affects Zebrafish Embryonic Development through a p53-Dependent Apoptotic Response

Ribosome is responsible for protein synthesis in all organisms and ribosomal proteins (RPs) play important roles in the formation of a functional ribosome. L11 was recently shown to regulate p53 activity through a direct binding with MDM2 and abrogating the MDM2-induced p53 degradation in response to ribosomal stress. However, the studies were performed in cell lines and the significance of this tumor suppressor function of L11 has yet to be explored in animal models. To investigate the effects of the deletion of L11 and its physiological relevance to p53 activity, we knocked down the rpl11 gene in zebrafish and analyzed the p53 response. Contrary to the cell line-based results, our data indicate that an L11 deficiency in a model organism activates the p53 pathway. The L11-deficient embryos (morphants) displayed developmental abnormalities primarily in the brain, leading to embryonic lethality within 6–7 days post fertilization. Extensive apoptosis was observed in the head region of the morphants, thus correlating the morphological defects with apparent cell death. A decrease in total abundance of genes involved in neural patterning of the brain was observed in the morphants, suggesting a reduction in neural progenitor cells. Upregulation of the genes involved in the p53 pathway were observed in the morphants. Simultaneous knockdown of the p53 gene rescued the developmental defects and apoptosis in the morphants. These results suggest that ribosomal dysfunction due to the loss of L11 activates a p53-dependent checkpoint response to prevent improper embryonic development

p53 and p73: seeing double?

Whereas p73 is closely related to the tumour-suppressor protein p53, its contribution to tumour suppression and the spatial and temporal regulation of its isoforms is unclear. It has now been established that p73 is a transcriptional target of E2F1. Its ability to induce apoptosis in TP53(-/-) cells indicates a tumour-control mechanism that runs parallel to but independent of that mediated by p53. The new results illustrate a complex cross-talk between p53, E2F1 and p73

Knowing me, knowing you : own orientation and information about the

The purpose of this study was to examine the effects of motivational orientations on negotiation outcomes in unstable negotiation contexts. Instability was created by pitting individualists against cooperators (mixed dyads), and by giving only one of the parties information about the other party’s orientation. A total of 162 subjects participated in negotiation simulations, where orientation and information were manipulated through instructions from management. The cooperative dyads got better outcomes than did the individualistic dyads. The mixed dyads did as well as the cooperative dyads when the cooperators had information, but did as badly as the individualistic dyads when the individualists had information. The process analyses indicated that the dyads with high outcomes achieved their results because the integrative activities increased over time. In the mixed dyads with informed individualists, the individualists reached higher individual outcome than their cooperative (uninformed) opponents. Thus, naive cooperators can easily be exploited

Ribosomal 18 S RNA Processing by the IGF-I-responsive WDR3 Protein Is Integrated with p53 Function in Cancer Cell Proliferation*

Insulin-like growth factor-I (IGF-I) signaling is strongly associated with cell growth and regulates the rate of synthesis of the rRNA precursor, the first and the key stage of ribosome biogenesis. In a screen for mediators of IGF-I signaling in cancer, we recently identified several ribosome-related proteins, including NEP1 (nucleolar essential protein 1) and WDR3 (WD repeat 3), whose homologues in yeast function in ribosome processing. The WDR3 gene and its locus on chromosome 1p12-13 have previously been linked with malignancy. Here we show that IGF-I induces expression of WDR3 in transformed cells. WDR3 depletion causes defects in ribosome biogenesis by affecting 18 S rRNA processing and also causes a transient down-regulation of precursor rRNA levels with moderate repression of RNA polymerase I activity. Suppression of WDR3 in cells expressing functional p53 reduced proliferation and arrested cells in the G1 phase of the cell cycle. This was associated with activation of p53 and sequestration of MDM2 by ribosomal protein L11. Cells lacking functional p53 did not undergo cell cycle arrest upon suppression of WDR3. Overall, the data indicate that WDR3 has an essential function in 40 S ribosomal subunit synthesis and in ribosomal stress signaling to p53-mediated regulation of cell cycle progression in cancer cells