Cellular and Molecular Life Sciences

, Volume 65, Issue 14, pp 2232–2243 | Cite as

Kuz and TACE can activate Notch independent of ligand

Research Article

Abstract.

A central mechanism in activation of the Notch signaling pathway is cleavage of the Notch receptor by ADAM metalloproteases. ADAMs also cleave Delta, the ligand for Notch, thereby downregulating Notch signals. Two ADAMs, Kuzbanian (Kuz) and TNF-α converting enzyme (TACE), are known to process both Delta and Notch, yet the role of these cleavages in signal propagation has remained controversial. Using an in vitro model, we show that Kuz regulates Notch signaling primarily by activating the receptor and has little overall effect on signaling via disabling Delta. We confirm that Kuz-dependent activation of Notch requires stimulation of Notch by Delta. However, over-expression of Kuz gives ligand-independent Notch activation. In contrast, TACE, which is elevated in expression in the developing Drosophila nervous system, can efficiently activate Notch in a ligand-independent manner. Altogether, these data demonstrate the potential for Kuz and TACE to participate in context- and mechanism-specific modes of Notch activation.

Keywords.

Notch Delta ADAM protease Kuzbanian TACE proteolysis 

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Copyright information

© Birkhaueser 2008

Authors and Affiliations

  1. 1.Department of Anatomy and NeurobiologyUniversity of VermontBurlingtonUSA

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