Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published November 30, 2018 | Accepted Version + Supplemental Material
Journal Article Open

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


In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. In contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids. This up-regulation strictly required the Gcn2 kinase, which phosphorylates Fmt1 and mediates its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins act as fMet/N-degrons, and identified the Psh1 ubiquitin ligase as the recognition component of this eukaryotic fMet/N-end rule pathway, which destroys Nt-formylated proteins.

Additional Information

© 2018 American Association for the Advancement of Science. We thank W.-K. Huh (Seoul National University, Seoul, Korea) for yeast deletion library mutants, S. Biggins (Hutchinson Cancer Center, Seattle, WA, USA) for pSB1535 and pSB1541, and R. Sauer (MIT, Cambridge, MA, USA) for AG110A(DE) E. coli. We also thank the present and former members of the Hwang laboratory for their assistance and advice. Supported by grants from the Samsung Science & Technology Foundation (SSTF-BA1401-17) and the BK21 plus program (C.-S.H.), by the NRF grants of the Korean Government (MSIP) NRF-2017M3A9F9030559 (C.L.) and NRF-2017R1A5A1015366 (J.-Y.Y.), and by NIH grants R01GM031530 and R01DK039520 (A.V.). Author contributions: C.-S.H., J.-M.K., J.-Y.Y., C.L., A.V., and other coauthors designed research. J.-M.K., O.-H.S., S.J., J.-E.H., J.Y., D.-S.K. and C.-S.H. performed research, and all coauthors analyzed data. C.-S.H., J.-M.K., C.L. and A.V. wrote the paper. All coauthors declare no competing interests. Data and materials availability: All mass spectrometric data of this study are available in PRIDE database (accession number: PXD010780). All (other) data needed to evaluate the conclusions in the paper are present in the paper or the Supplementary Materials.

Attached Files

Accepted Version - nihms-1029362.pdf

Supplemental Material - aat0174_Kim_SM.pdf


Files (6.9 MB)
Name Size Download all
5.1 MB Preview Download
1.9 MB Preview Download

Additional details

August 19, 2023
October 19, 2023