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Bound for destruction: Ubiquitination protects against improper Notch signaling

The Notch pathway is an important molecular signaling mechanism whose existence has been known, or at least hinted at, for nearly a century since the identification of a mutant strain of Drosophila fruit flies with “notched?wings in Thomas Hunt Morgan’s lab in 1910. Later studies revealed that the Notch gene encodes a receptor protein that extends through both sides of the cell membrane and which is capable of interacting with a ligand partner, such as the protein Delta, presented on the surface of a neighboring cell. This “juxtracrine?interaction causes the cleavage of an intracellular region of the Notch protein, loosing it into the cytoplasm and triggering the activation of transcription factors within the cell’s nucleus. In addition to its effects on wing structure in flies, Notch signaling is known to be important in a number of neural cell fate determination and developmental processes, and is conserved in species from human to roundworm. In all processes in which it participates, Notch signaling shows the ability to sense a small change in cell fate and amplify it, acting as a sort of contrast enhancement mechanism in cell fate determination.

Notch is activated by a protease that is present ubiquitously in the cell membrane. What has long remained a mystery, however, is the question of how Notch receptors that have not been activated by a ligand are protected from digestion by that protease. Now, in a report published in the December 29 issue of Current Biology, Shigeo Hayashi (Group Director, Laboratory for Morphogenetic Signaling) and colleagues at the RIKEN Center for Developmental Biology (Kobe, Japan) have identified the means by which unstimulated cells protect the Notch receptor from activation. Recent studies by other labs had shown that a number of stages in the Notch cascade were subject to ubiquitination, in which proteins are tagged by a complex of ubiquitin proteins. This system is
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Source:Riken Center for Developmental Biology


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