Ubiquitination of the heterotrimeric G protein α subunits Gαi2 and Gαq is prevented by the guanine nucleotide exchange factor Ric-8A
Ubiquitination of the heterotrimeric G protein α subunits Gαi2 and Gαq is prevented by the guanine nucleotide exchange factor Ric-8A
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DOI：
10.1016/j.bbrc.2013.04.103
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发表时间：
2013-06-07
影响因子：
3.1
通讯作者：
Sumimoto, Hideki
中科院分区：
文献类型：
--
作者：
Chishiki, Kanako;Kamakura, Sachiko;Sumimoto, Hideki
胞浆蛋白Ric-8A在体外充当异三聚体G蛋白的GI、Gq和G12/13类别的G α亚基的鸟嘌呤核苷酸交换因子，并且还已知可以增加这些G α蛋白在体内的量。然而，Ric-8调节G α含量的机制尚未完全了解。在这里，我们表明Ric-8通过阻止G α i2和G α q的泛素化来稳定G α i2和G α q。当在COS-7细胞中表达时，Ric-8A与G α i2、G α q、G α 12相互作用并使其稳定，但不与G α s相互作用并使其稳定。G α i2和G α q的蛋白质水平似乎是通过泛素-蛋白酶体降解途径控制的，因为这些G α亚基经历多聚泛素化并被蛋白酶体抑制剂MG 132稳定。Ric-8A的表达抑制G α i2和G α q的泛素化。这种抑制可能需要Ric-8A与这些G α蛋白的相互作用：G α q和G α i2的C末端截短完全消除了它们与Ric-8A的相互作用、它们被Ric-8A稳定以及Ric-8A介导的G α泛素化抑制。(C)2013 Elsevier Inc. All rights reserved.
The cytosolic protein Ric-8A acts as a guanine nucleotide exchange factor for G alpha 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 alpha proteins in vivo. The mechanism whereby Ric-8 regulates G alpha content, however, has not been fully understood. Here we show that Ric-8 Astabilizes G alpha i2 and G alpha q by preventing their ubiquitination. Ric-8A interacts with and stabilizes G alpha i2, G alpha q, G alpha 12, but not G alpha s, when expressed in COS-7 cells. The protein levels of G alpha i2 and G alpha q appear to be controlled via the ubiquitin-proteasome degradation pathway, because these G alpha subunits undergo polyubiquitination and are stabilized with the proteasome inhibitor MG132. The ubiquitination of G alpha i2 and G alpha q is suppressed by expression of Ric-8A. The suppression likely requires Ric-8A interaction with these G alpha proteins: the C-terminal truncation of G alpha q and G alpha i2 completely abrogates their interaction with Ric-8A, their stabilization by Ric-8A, and Ric-8A-mediated inhibition of G alpha ubiquitination. (C) 2013 Elsevier Inc. All rights reserved.