Activities

Mitotic Wnt signaling promotes protein stabilization and regulates cell size

 

Seminar

Mitotic Wnt signaling promotes protein stabilization and regulates cell size

Sergio Pérez Acebrón, PhD

Mitotic Wnt signaling promotes protein stabilization and regulates cell size The Wnt signaling pathway is a major regulator of cell fate and tissue homeostasis in numerous organs. Its misregulation is a frequent cause of disease, notably cancer. Canonical Wnt signaling is thought to regulate cell behavior mainly by inducing β-catenin-dependent transcription of target genes. We discovered a Wnt-dependent stabilization of proteins (Wnt/STOP), which is independent of β-catenin and peaks during mitosis. We show that Wnt/STOP plays a critical role in protecting proteins, including MYC, from GSK3-dependent polyubiquitination and degradation. Wnt/STOP signaling increases cellular protein levels and cell size. Wnt/STOP rather than β-catenin signaling is the dominant mode of Wnt signaling in several cancer cell lines, where it is required for cell growth. We propose that Wnt/STOP signaling slows down protein degradation as cells prepare to divide.