Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency

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Growth of all living things relies on protein synthesis. Failure of components of the complex protein synthesis machinery underlies a growing list of inherited and acquired multi—organ syndromes referred to as ribosomopathies. While ribosomes, the critical working components of the protein synthesis machinery, are required in all cell types to translate the genetic code, only certain organs manifest clinical symptoms in ribosomopathies, indicating specific cell-type features of protein synthesis control. Further, many of these diseases result in cancer despite an inherent deficit in growth. Here we report a range of consequences of protein synthesis insufficiency with loss of a broadly expressed ribosome factor, leading to growth impairment and cell cycle arrest at different stages. Apparent induction of p53-dependent cell death and arrest pathways included apoptosis in the fetal brain and senescence in the mature exocrine pancreas. The senescence, considered a tumour suppression mechanism, was accompanied by the expression of biomarkers associated with early stages of malignant transformation. These findings inform how cancer may initiate when growth is compromised and provide new insights into cell-type specific consequences of protein synthesis insufficiency.

Vyšlo v časopise: Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005288
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005288

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