Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 7 November 2008:
Vol. 322. no. 5903, pp. 923 - 929
DOI: 10.1126/science.1160462
Prev | Table of Contents | Next

Research Articles

Identification of SCF Ubiquitin Ligase Substrates by Global Protein Stability Profiling

Hsueh-Chi Sherry Yen and Stephen J. Elledge*

Ubiquitin-mediated proteolysis regulates all aspects of cellular function, and defects in this process are associated with human diseases. The limited number of identified ubiquitin ligase–substrate pairs is a major bottleneck in the ubiquitin field. We established and applied genetic technologies that combine global protein stability (GPS) profiling and genetic perturbation of E3 activity to screen for substrates of the Skp1–cullin–F-box (SCF) ubiquitin ligase in mammalian cells. Among the >350 potential substrates identified, we found most known SCF targets and many previously unknown substrates involved in cell cycle, apoptosis, and signaling pathways. Exploring cell cycle–stage stability, we found that several substrates used the SCF and other E3s in different cell cycle stages. Our results demonstrate the potential of these technologies as general platforms for the global discovery of E3-substrate regulatory networks.

Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: selledge{at}genetics.med.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cullin 1 Functions as a Centrosomal Suppressor of Centriole Multiplication by Regulating Polo-like Kinase 4 Protein Levels.
N. Korzeniewski, L. Zheng, R. Cuevas, J. Parry, P. Chatterjee, B. Anderton, A. Duensing, K. Munger, and S. Duensing (2009)
Cancer Res. 69, 6668-6675
   Abstract »    Full Text »    PDF »
ROC1/RBX1 E3 Ubiquitin Ligase Silencing Suppresses Tumor Cell Growth via Sequential Induction of G2-M Arrest, Apoptosis, and Senescence.
L. Jia, M. S. Soengas, and Y. Sun (2009)
Cancer Res. 69, 4974-4982
   Abstract »    Full Text »    PDF »
Global Protein Stability Profiling in Mammalian Cells.
H.-C. S. Yen, Q. Xu, D. M. Chou, Z. Zhao, and S. J. Elledge (2008)
Science 322, 918-923
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)