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Mol Cell. 2014 May 22;54(4):663-74. doi: 10.1016/j.molcel.2014.04.014. Epub 2014 May 15.

Mitotic wnt signaling promotes protein stabilization and regulates cell size.

Author information

1
DKFZ-ZMBH Alliance, Division of Molecular Embryology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Electronic address: s.perezacebron@dkfz-heidelberg.de.
2
Institute of Molecular Biology, Ackermannweg 4, D-55128 Mainz, Germany.
3
DKFZ-ZMBH Alliance, Division of Molecular Embryology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
4
DKFZ-ZMBH Alliance, Division of Molecular Embryology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; Institute of Molecular Biology, Ackermannweg 4, D-55128 Mainz, Germany. Electronic address: niehrs@dkfz-heidelberg.de.

Abstract

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.

PMID:
24837680
DOI:
10.1016/j.molcel.2014.04.014
[Indexed for MEDLINE]
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