Sign up for Table of Contents Alerts.
Email this page
Print this page
Perspectives
Mechanisms of Tumor Suppression by the SCFFbw7
Alex C. Minella and Bruce E. Clurman
volume 4 | issue 10
october 2005Pages: 1356 - 1359
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
SCF ubiquitin ligases regulate the degradation of many proteins involved in the control of cell division and growth. F-box proteins are the SCF components that bind to substrates, and this binding is usually signaled by substrate phosphorylation. The Fbw7/hCdc4 F-box protein was first recognized by its binding to cyclin E, and the SCFFbw7 is now known to target c-Myc, c-Jun and Notch for degradation, in addition to its role in cyclin E proteolysis. Fbw7 thus negatively regulates several key oncoproteins. Accordingly, Fbw7 is a tumor suppressor that is mutated in a wide spectrum of human cancers, and Fbw7 functions as a haploinsufficient tumor suppressor in mice. Because there are three Fbw7 isoforms that reside in different subcellular compartments, as well as multiple Fbw7 substrates that are the products of protooncogenes, the mechanisms of tumor suppression by Fbw7 are complex and incompletely understood. In this review we discuss the activities of the SCFFbw7 in the context of its role as a tumor suppressor and highlight recent findings demonstrating that dominant oncogenes disable Fbw7 function.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.