Notch1 Signaling is Mediated by Importins Alpha 3, 4, and 7

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2010 May 11

PMID 20454918

Citations 35

Authors

Kerstin Huenniger

Andreas Kramer

Malle Soom

Iree Chang

Matthias Kohler

Reinhard Depping

Ralph H Kehlenbach

Christoph Kaether

Affiliations

Soon will be listed here.

Abstract

The Notch signaling pathway is an important regulation system for the development and self-renewal of different tissues. A specific feature of this signaling cascade is the function of Notch as a surface receptor and regulator of gene expression. Hence, Notch activation and signal transduction requires the proteolytic release of the Notch intracellular domain (NICD), which activates the transcription of cell-specific genes after its transport into the nucleus. To date, little is known about the mechanisms that mediate NICD nuclear import. We here show that transport of NICD into the nucleus is mediated by the canonical importin alpha/beta1 pathway. GST pull-down experiments revealed that NICD binds via one of its four potential nuclear localization signals to importins alpha3, alpha4, and alpha7, but not to alpha1 and alpha5. siRNA-mediated knockdown experiments showed that importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of NICD and thus are directly involved in Notch signaling.

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