Abstract
Signalling activity of the Notch receptor, which plays a fundamental role in metazoan cell fate determination, is controlled at multiple levels. We uncovered a Notch signal-controlling mechanism that depends on the ability of the non-visual beta-arrestin, Kurtz (Krz), to influence the degradation and, consequently, the function of the Notch receptor. We identified Krz as a binding partner of a known Notch-pathway modulator, Deltex (Dx), and demonstrated the existence of a trimeric Notch-Dx-Krz protein complex. This complex mediates the degradation of the Notch receptor through a ubiquitination-dependent pathway. Our results establish a novel mode of regulation of Notch signalling and define a new function for non-visual beta-arrestins.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arrestins / genetics
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Arrestins / metabolism
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Arrestins / physiology*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila Proteins / physiology
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Female
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Male
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Multiprotein Complexes
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Mutation / physiology
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Receptors, Notch / metabolism*
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Signal Transduction*
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Two-Hybrid System Techniques
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Ubiquitin / metabolism
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Wings, Animal / growth & development
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beta-Arrestins
Substances
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Arrestins
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DX protein, Drosophila
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Drosophila Proteins
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Membrane Proteins
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Multiprotein Complexes
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N protein, Drosophila
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Receptors, Notch
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Ubiquitin
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beta-Arrestins
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krz protein, Drosophila