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Published May 23, 2013 | Accepted Version + Supplemental Material
Journal Article Open

Control of Protein Quality and Stoichiometries by N-Terminal Acetylation and the N-End Rule Pathway


N^α-terminal acetylation of cellular proteins was recently discovered to create specific degradation signals termed Ac/N-degrons and targeted by the Ac/N-end rule pathway. We show that Hcn1, a subunit of the APC/C ubiquitin ligase, contains an Ac/N-degron that is repressed by Cut9, another APC/C subunit and the ligand of Hcn1. Cog1, a subunit of the Golgi-associated COG complex, is also shown to contain an Ac/N-degron. Cog2 and Cog3, direct ligands of Cog1, can repress this degron. The subunit decoy technique was used to show that the long-lived endogenous Cog1 is destabilized and destroyed via its activated (unshielded) Ac/N-degron if the total level of Cog1 increased in a cell. Hcn1 and Cog1 are the first examples of protein regulation through the physiologically relevant transitions that shield and unshield natural Ac/N-degrons. This mechanistically straightforward circuit can employ the demonstrated conditionality of Ac/N-degrons to regulate subunit stoichiometries and other aspects of protein quality control.

Additional Information

© 2013 Elsevier Inc. Received: January 30, 2013. Revised: March 4, 2013. Accepted: March 12, 2013. Published: April 18, 2013. We thank R. Deshaies and K. Gould for gifts of plasmids. We are grateful to the present and former members of the Varshavsky laboratory for their assistance and advice. This work was supported by grants to C.-S.H. from the (NRF-2011-0021975) and the Korea Healthcare Technology R&D Project (A111324), and to A.V. from the National Institutes of Health (DK039520, GM031530, and GM085371).

Attached Files

Accepted Version - nihms459764.pdf

Supplemental Material - mmc1.pdf


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