Negative-feedback regulation of the Wnt pathway by conductin/axin2 involves insensitivity to upstream signalling.

Axin and conductin (also known as axin2) are structurally related inhibitors of Wnt/β-catenin signalling that promote degradation of β-catenin. Whereas axin is constitutively expressed, conductin is a Wnt target gene implicated in Wnt negative-feedback regulation. Here, we show that axin and conductin differ in their functional interaction with the upstream Wnt pathway component Dvl. Conductin shows reduced binding to Dvl2 compared to axin, and degradation of β-catenin by conductin is only poorly blocked by Dvl2. We propose that insensitivity to Dvl is an important feature of the role of conductin as a negative-feedback regulator of Wnt signalling.