The Deubiquitinating Enzyme USP17 Blocks N-Ras Membrane Trafficking and Activation but Leaves K-Ras Unaffected

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.

Global Governance and International Migration: A Case Study of Trafficking of Human Beings

The purpose of this article is to explore the concept of “global governance” and the way it applies to the management of international migration by using trafficking of human beings as a case study. Globalization has altered the scene of world politics. A traditional State-centric view of the world order has been overshadowed by the increasing importance of other actors, including the United Nations, multi-national corporations and non-governmental organizations. Globalization has also altered the dynamics of rule making and their enforcement within the international system, in that not only States but also these non-State actors exercise enormous influence. The concept of global governance acknowledges this as it aims to include all the pertinent actors involved. To illustrate this further, the author will use trafficking of human beings as a case study. Two key principles of global governance are participation and accountability. This article will analyse how these principles are reflected and implemented in the regime dealing with the prevention and suppression of trafficking of human beings.