Proteasomal degradation of cytotoxic necrotizing factor 1-activated Rac
Proteasomal degradation of cytotoxic necrotizing factor 1-activated Rac
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DOI：
10.1128/iai.70.8.4053-4058.2002
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发表时间：
2002-08-01
影响因子：
3.1
通讯作者：
Schmidt, G
中科院分区：
文献类型：
--
作者：
Lerm, M;Pop, M;Schmidt, G
来自大肠杆菌的细胞毒性坏死因子 1 (CNF1) 已被证明可以通过谷氨酰胺 63 的脱酰胺作用来激活 Rho 家族的成员。该氨基酸对于 GTP 的水解至关重要，任何取代都会产生组成型活性 Rho。 Rho 的激活分别由于 RhoA、Cdc42 和 Rac 的激活而诱导应力纤维、丝状伪足和膜褶边的形成。在这里，我们发现 CNF1 处理的 HEK293 和 HeLa 细胞中内源性 Rac 水平降低。 mRNA 的量未受影响，因此 Rac 可能会被蛋白水解降解。用乳胞素（26S 蛋白酶体抑制剂）处理细胞可防止 Rac 降解。我们之前已经证明，CNF1 仅在 HeLa 细胞中短暂激活 c-Jun N 末端激酶 (JNK) (M. Lerm, J. Selzer, A. Hoffmeyer, U. R. Rapp, K. Aktories, and G. Schmidt, Infect. Immun. 67:496-503, 1998)。在这里，我们表明 CNF1 诱导的 JNK 激活在乳胞素存在的情况下稳定。数据表明，在 CNF1 处理的细胞中，Rac 通过蛋白酶体依赖性途径降解。
The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli has been shown to activate members of the Rho family by deamidation of glutamine 63. This amino acid is essential for hydrolysis of GTP, and any substitution results in a constitutively active Rho. Activation of Rho induces the formation of stress fibers, filopodia, and membrane ruffles due to activation of RhoA, Cdc42, and Rac, respectively. Here we show that the level of endogenous Rac decreased in CNF1-treated HEK293 and HeLa cells. The amount of mRNA remained unaffected, leaving the possibility that Rac is subject to proteolytic degradation. Treatment of cells with lactacystin, an inhibitor of the 26S proteasome, protected Rac from degradation. We have previously shown that CNF1 activates the c-Jun N-terminal kinase (JNK) only transiently in HeLa cells (M. Lerm, J. Selzer, A. Hoffmeyer, U. R. Rapp, K. Aktories, and G. Schmidt, Infect. Immun. 67:496-503, 1998). Here we show that CNF1-induced JNK activation is stabilized in the presence of lactacystin. The data indicate that Rac is degraded by a proteasome-dependent pathway in CNF1-treated cells.