Research Article

Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway

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Science  30 Nov 2018:
Vol. 362, Issue 6418, eaat0174
DOI: 10.1126/science.aat0174

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Another N-end rule to add

Proteins that emerge from a ribosome bear the N-terminal methionine (Met) residue. In bacteria, Met is formylated before translation starts, whereas in eukaryotes, most nascent proteins seemed to start with unmodified Met. Working in yeast, Kim et al. found that the N-terminal formylation of eukaryotic proteins is detectable even under normal conditions and is greatly increased upon specific stresses, which cause some Fmt1 formyltransferase to be retained in the cytoplasm. The retention of this normally mitochondrial protein was found to require the Gcn2 kinase. In addition, the Psh1 ubiquitin ligase was shown to target N-terminally formylated eukaryotic proteins for proteasome-dependent degradation by the so-called fMet/N-end rule pathway.

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