Mitotic wnt signaling promotes protein stabilization and regulates cell size.
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.
DKFZ-ZMBH Alliance, Division of Molecular Embryology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Electronic address: s.perezacebron@dkfz-heidelberg.de.
Sergio P
SP
Acebron
Institute of Molecular Biology, Ackermannweg 4, D-55128 Mainz, Germany.
Emil
E
Karaulanov
DKFZ-ZMBH Alliance, Division of Molecular Embryology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Birgit S
BS
Berger
DKFZ-ZMBH Alliance, Division of Molecular Embryology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Ya-Lin
YL
Huang
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.
Christof
C
Niehrs
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048429:Cell Size; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D040081:Protein Array Analysis; D055550:Protein Stability; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051153:Wnt Proteins; D038362:Glycogen Synthase Kinase 3