Ubiquitination of the heterotrimeric G protein ¦Á subunits G¦Ái2 and G¦Áq is prevented by the guanine nucleotide exchange factor Ric-8A

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• 作者：Kanako Chishiki ; Sachiko Kamakura ; Satoru Yuzawa ; Junya Hayase ; Hideki Sumimoto ; ^{hsumi@med.kyushu-u.ac.jp}
• 关键词：GPCR ; G-protein-coupled receptor ; GEF ; guanine nucleotide exchange ; CHX ; cycloheximide
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：7 June, 2013
• 年：2013
• 卷：435
• 期：3
• 页码：414-419
• 全文大小：1552 K

文摘

The cytosolic protein Ric-8A acts as a guanine nucleotide exchange factor for G¦Á subunits of the Gi, Gq, and G12/13 classes of heterotrimeric G protein in vitro, and is also known to increase the amounts of these G¦Á proteins in vivo. The mechanism whereby Ric-8 regulates G¦Á content, however, has not been fully understood. Here we show that Ric-8 Astabilizes G¦Ái2 and G¦Áq by preventing their ubiquitination. Ric-8A interacts with and stabilizes G¦Ái2, G¦Áq, G¦Á12, but not G¦Ás, when expressed in COS-7 cells. The protein levels of G¦Ái2 and G¦Áq appear to be controlled via the ubiquitin-proteasome degradation pathway, because these G¦Á subunits undergo polyubiquitination and are stabilized with the proteasome inhibitor MG132. The ubiquitination of G¦Ái2 and G¦Áq is suppressed by expression of Ric-8A. The suppression likely requires Ric-8A interaction with these G¦Á proteins; the C-terminal truncation of G¦Áq and G¦Ái2 completely abrogates their interaction with Ric-8A, their stabilization by Ric-8A, and Ric-8A-mediated inhibition of G¦Á ubiquitination.