Mitotic Wnt Signaling Promotes Protein Stabilization and Regulates Cell Size

• Published in: Molecular cell Vol. 54; no. 4; pp. 663 - 674
• Main Authors: Acebron, Sergio P., Karaulanov, Emil, Berger, Birgit S., Huang, Ya-Lin, Niehrs, Christof
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-05-2014
• Subjects: Cell Line, Tumor; Cell Proliferation; Cell Size; Gene Expression Regulation; Glycogen Synthase Kinase 3 - metabolism; HEK293 Cells; HeLa Cells; Humans; Mitosis; Protein Array Analysis; Protein Stability; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Ubiquitination; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Signaling Pathway
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2014.04.014

Canonical Wnt signaling is thought to regulate cell behavior mainly by inducing β-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 β-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 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.
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•Wnt signaling stabilizes proteins in mitosis (Wnt/STOP signaling)•Wnt/STOP signaling is β-catenin independent•Wnt/STOP stabilizes c-MYC•Wnt/STOP signaling increases cellular protein levels and cell size
Wnt signaling is thought to regulate cell behavior mainly by transcription of target genes. Acebron et al. show that Wnt signaling slows down protein degradation as cells prepare to divide. This Wnt-dependent stabilization of proteins (Wnt/STOP) is independent of transcription and increases cell size.