While viral inhibition by tethering of budding virions to host cell membranes has been focused upon as one of the main functions of BST-2/tetherin, BST-2 is thought to possess other functions as well. Overexpression of BST-2 was found here to down-regulate transient protein expression. Removal of the N- and C-terminal regions of BST-2, previously described to be involved in signal transduction, reduced the impact of BST-2. These results suggest that BST-2-mediated signaling may play a role in regulating the levels of transiently expressed proteins, highlighting a new function for BST-2 that may also have implications for viral inhibition. (C) 2014 Elsevier Inc. All rights reserved.