β-Arrestin Regulates Notch Abundance

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Science  23 Dec 2005:
Vol. 310, Issue 5756, pp. 1873
DOI: 10.1126/science.310.5756.1873c

β-Arrestin, well known for its role in G protein-coupled receptor regulation, is also being recognized for its roles in regulating other types of receptors. Mukherjee et al. report that Drosophila β-arrestin, Kurtz (Krz), is involved in controlling the abundance of the receptor Notch. Notch is a single transmembrane receptor that is cleaved in response to ligand binding, releasing a fragment that translocates to the nucleus to regulate transcription. Krz was found in two different screens for proteins that interacted with the Notch regulator and with putative E3 ubiquitin ligase Deltex (Dx). In flies, loss of Krz function led to increased Notch abundance. Overexpression of both Krz and Dx produced Notch loss-of-function phenotypes and reduced Notch protein abundance. In transfected Drosophila S2 cells, Krz and Dx together promoted ubiquitination of Notch. Notch signaling is highly sensitive to gene dosage effects, and β-arrestin appears to be one component that contributes to this sensitivity. — NG

Nat. Cell Biol. 7, 1191 (2005).

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