p53- and ERK7-Dependent Ribosome Surveillance Response Regulates Insulin-Like Peptide Secretion

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Ribosome biogenesis is a major consumer of cellular energy and a rate-limiting process during cell growth. The ribosome biogenesis pathway is tightly connected with signaling pathways that regulate tissue growth. For example, nutrient-regulated signaling cues adjust the rate of ribosome biogenesis. On the other hand, the process of ribosome biogenesis is closely monitored by so-called surveillance mechanisms. The best-known ribosome surveillance factor is the transcription factor and tumor suppressor p53. In proliferating cells, activation of p53 upon disturbed ribosome biogenesis leads to cell cycle arrest and inhibition of proliferation. Here we show that ribosome surveillance not only regulates growth locally in proliferating cells, but is also coupled to hormonal growth control through regulation of insulin like peptide (dILPs) secretion. We observed that inhibition of ribosome biogenesis in the Drosophila insulin-producing cells generates a strong cell autonomous signal to inhibit dILP secretion. We identify two downstream effectors of this ribosome surveillance response by showing that p53 as well as an atypical MAP kinase ERK7 are mediators of the inhibition of dILP secretion. We also provide evidence that this ribosome surveillance mechanism contributes to nutrient-dependent regulation of dILP secretion.

Vyšlo v časopise: p53- and ERK7-Dependent Ribosome Surveillance Response Regulates Insulin-Like Peptide Secretion. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004764
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004764

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