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

Shemorry, Anna and Hwang, Cheol-Sang and Varshavsky, Alexander (2013) Control of Protein Quality and Stoichiometries by N-Terminal Acetylation and the N-End Rule Pathway. Molecular Cell, 50 (4). pp. 540-551. ISSN 1097-2765. PMCID PMC3665649. doi:10.1016/j.molcel.2013.03.018.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Hwang, Cheol-Sang0000-0002-0105-5957
Varshavsky, Alexander0000-0002-4011-258X
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).
Funding AgencyGrant Number
National Research Foundation of KoreaNRF-2011-0021975
Korea Healthcare Technology R&D ProjectA111324
Issue or Number:4
PubMed Central ID:PMC3665649
Record Number:CaltechAUTHORS:20130716-134300224
Persistent URL:
Official Citation:Anna Shemorry, Cheol-Sang Hwang, Alexander Varshavsky, Control of Protein Quality and Stoichiometries by N-Terminal Acetylation and the N-End Rule Pathway, Molecular Cell, Volume 50, Issue 4, 23 May 2013, Pages 540-551, ISSN 1097-2765, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39397
Deposited By: Ruth Sustaita
Deposited On:16 Jul 2013 20:59
Last Modified:09 Nov 2021 23:44

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