Notch1 signaling is mediated by importins alpha 3, 4, and 7

Kerstin Huenniger, Andreas Krämer, Malle Soom, Iree Chang, Matthias Köhler, Reinhard Depping, Ralph H. Kehlenbach, Christoph Kaether*

*Corresponding author for this work
37 Citations (Scopus)


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 α/β1 pathway. GST pull-down experiments revealed that NICD binds via one of its four potential nuclear localization signals to importins α3, α4, and α7, but not to α1 and α5. siRNA-mediated knockdown experiments showed that importins α3, α4 (and to a lesser extent, α7) mediate nuclear import of NICD and thus are directly involved in Notch signaling.

Original languageEnglish
JournalCellular and Molecular Life Sciences
Issue number18
Pages (from-to)3187-3196
Number of pages10
Publication statusPublished - 09.2010

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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