Sci. STKE, 25 September 2001
Ubiquitination Notch Interacts with an E3 Ligase
The membrane protein Notch transduces signals from the cell surface to the transcription machinery by deploying its cleaved intracellular (IC) domain to the nucleus. It is less clear how Notch action is turned off once its mission is fulfilled in the nucleus. Two groups now report that Notch activity may be terminated when the IC domain is proteolyzed as a result of being ubiquitinated by an E3 ligase called Sel-10. Genetic evidence drawn from the Caenorhabditis elegans homolog had suggested that Sel-10 negatively regulates Notch action. Gupta-Rossi et al. and Oberg et al. cloned the mammalian homologs and demonstrated that Sel-10 binds to and ubiquitinates the Notch IC domain. When proteolysis was inhibited by either expressing a dominant negative form of Sel-10 or by exposing cells to proteosome inhibitors, Notch IC accumulated in the cell, and transcription of a target reporter gene increased. This rapid mechanism of protein turnover may explain why the nuclear form of Notch has been difficult to detect.
N. Gupta-Rossi, O. Le Bail, H. Gonen, C. Brou, F. Logeat, E. Six, A. Ciechanover, A. Israel, Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. J. Biol. Chem. 276, 34371-34378 (2001). [Abstract] [Full Text]
C. Oberg, J. Li, A. Pauley, E. Wolf, M. Gurney, U. Lendahl, The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog. J Biol. Chem. 276, 35847-35853 (2001). [Abstract] [Full Text]
Citation: Notch Interacts with an E3 Ligase. Sci. STKE 2001, tw345 (2001).
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