Ubiquitin Specific Peptidase 34 (USP34)

The Wnt pathway is a fundamental signalling pathway conserved in all animals, regulating growth, differentiation, embryonic development, and tissue homeostasis in adults. Wnt signalling is kept quiescent by ubiquitin-mediated degradation of the transcription factor β-catenin, orchestrated by a group of proteins called the Destruction Complex.

USP34 functions to positively regulate Wnt signalling, acting downstream of β-catenin stabilization. While characterizing USP34 discovered a new positive regulatory role for Axin in promoting signalling that is dependent on its nuclear localization. USP34 stabilizes the nuclear pool of Axin through regulating its ubiquitination and offers a potential strategy to target pathological Wnt signalling.