Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway

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Title
Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway
Author(s)
S E Park; J M Kim; O H Seok; H Cho; B Wadas; Seon-Young Kim; A Varshavsky; C S Hwang
Bibliographic Citation
Science, vol. 347, no. 6227, pp. 1249-1252
Publication Year
2015
Abstract
Rgs2, a regulator of G proteins, lowers blood pressure by decreasing signaling through Gαq. Human patients expressing Met-Leu-Rgs2 (ML-Rgs2) or Met-Arg-Rgs2 (MR-Rgs2) are hypertensive relative to people expressing wild-type Met-Gln-Rgs2 (MQ-Rgs2). We found that wild-type MQ-Rgs2 and its mutant, MR-Rgs2, were destroyed by the Ac/N-end rule pathway, which recognizes Nα-terminally acetylated (Nt-acetylated) proteins. The shortest-lived mutant, ML-Rgs2, was targeted by both the Ac/N-end rule and Arg/N-end rule pathways. The latter pathway recognizes unacetylated N-terminal residues. Thus, the Nt-acetylated Ac-MX-Rgs2 (X = Arg, Gln, Leu) proteins are specific substrates of the mammalian Ac/N-end rule pathway. Furthermore, the Ac/N-degron of Ac-MQ-Rgs2 was conditional, and Teb4, an endoplasmic reticulum (ER) membrane-embedded ubiquitin ligase, was able to regulate G protein signaling by targeting Ac-MX-Rgs2 proteins for degradation through their Nα-terminal acetyl group.
ISSN
0036-8075
Publisher
Amer Assoc Advancement Science
DOI
http://dx.doi.org/10.1126/science.aaa3844
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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