Regulation of Notch signalling by non-visual β-arrestin

A Mukherjee, A Veraksa, A Bauer, C Rosse… - Nature cell …, 2005 - nature.com
A Mukherjee, A Veraksa, A Bauer, C Rosse, J Camonis, S Artavanis-Tsakonas
Nature cell biology, 2005nature.com
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 β-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 …
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 β-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 β-arrestins.
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