Translational Upregulation of an Individual p21 Transcript Variant by GCN2 Regulates Cell Proliferation and Survival under Nutrient Stress

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Cells sense nutrient levels in their environment in order to determine if conditions are favorable to divide. GCN2 is a protein that senses amino acids and responds to amino acid deficiency by suppressing protein synthesis and increasing the expression of genes involved in recovery from nutrient stress. Although GCN2’s role in amino acid sensing is well-characterized, it is not known how it links nutrient availability with the cell cycle. Here, we show that GCN2 induces the cell cycle inhibitor p21Cip1 at the level of protein translation. The induction of p21 is limited to a specific messenger RNA variant that contains upstream open reading frames, and these upstream open reading frames are required for its enhanced translation under stress. Previously, the functional significance of these different p21 variants was unknown. Upregulation of p21 allows cells to halt division and survive under conditions of nutrient stress. Collectively, this work demonstrates a new mechanism of p21 regulation and the connection between GCN2 and the cell cycle.

Vyšlo v časopise: Translational Upregulation of an Individual p21 Transcript Variant by GCN2 Regulates Cell Proliferation and Survival under Nutrient Stress. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005212
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005212

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