Mitotic Wnt Signaling Promotes Protein Stabilization and Regulates Cell Size

作者：Acebron Sergio P^*; Karaulanov Emil; Berger Birgit S; Huang Ya Lin; Niehrs Christof

来源：Molecular Cell, 2014, 54(4): 663-674.

DOI：10.1016/j.molcel.2014.04.014

Canonical Wnt signaling is thought to regulate cell behavior mainly by inducing beta-catenin-dependent transcription of target genes. In proliferating cells Wnt signaling peaks in the G2/M phase of the cell cycle, but the significance of this "mitotic Wnt signaling'' is unclear. Here we introduce Wnt-dependent stabilization of proteins (Wnt/STOP), which is independent of beta-catenin and peaks during mitosis. We show that Wnt/STOP plays a critical role in protecting proteins, including c-MYC, from GSK3-dependent polyubiquitination and degradation. Wnt/STOP signaling increases cellular protein levels and cell size. Wnt/STOP, rather than beta-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.

• 出版日期2014-5-22