Activity Detail
Seminar
Mitotic Wnt signaling promotes protein stabilization and regulates cell size
Sergio Pérez Acebrón, PhD
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.