The Deubiquitinating Enzyme USP17 Blocks N-Ras Membrane Trafficking and Activation but Leaves K-Ras Unaffected
The Deubiquitinating Enzyme USP17 Blocks N-Ras Membrane Trafficking and Activation but Leaves K-Ras Unaffected
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DOI：
10.1074/jbc.m109.081448
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发表时间：
2010-04-16
影响因子：
4.8
通讯作者：
Johnston, James A.
中科院分区：
文献类型：
--
作者：
de la Vega, Michelle;Burrows, James F.;Johnston, James A.
原癌基因RAS异构体(H、N和K)具有一个C端CAAX基序，并经历相同的翻译后处理步骤，尽管它们通过不同的途径运输到质膜。以前，我们已经证明了去泛素化酶USP17的过表达抑制了H-RAS在质膜上的定位。现在我们报道，在USP17存在下，H-RAS和N-RAS不能定位到质膜，而K-Ras4b的定位不受影响。EGF刺激不能诱导USP17表达细胞的N-RAS膜定位。此外，N-RAS活性和通过MAPK、MEK/ERK和PI3K/JNK途径的下游信号被钝化。然而，在表达USP17的细胞中，我们仍然检测到N-RAS在内质网和高尔基体中的丰富定位。总而言之，我们的数据显示，去泛素化酶USP17阻止了EGF诱导的N-RAS膜的运输和激活，但不影响K-RAS。
The proto-oncogenic Ras isoforms (H, N, and K) have a C-terminal CAAX motif and undergo the same post-translational processing steps, although they traffic to the plasma membrane through different routes. Previously, we have shown that overexpression of the deubiquitinating enzyme USP17 inhibits H-Ras localization to the plasma membrane. Now we report that whereas H-Ras and N-Ras were unable to localize to the plasma membrane in the presence of USP17, K-Ras4b localization was unaffected. EGF stimulation was unable to induce N-Ras membrane localization in USP17-expressing cells. In addition, N-Ras activity and downstream signaling through the MAPK MEK/ERK and PI3K/JNK pathways were blunted. However, we still detected abundant N-Ras localization at the ER and Golgi in USP17-expressing cells. Collectively, our data showed that the deubiquitinating enzyme USP17 blocks EGF-induced N-Ras membrane trafficking and activation, but left K-Ras unaffected.