Cell cycle control of Wnt/β-catenin signalling by conductin/axin2 through CDC20.
Wnt/β-catenin signalling regulates cell proliferation by modulating the cell cycle and is negatively regulated by conductin/axin2/axil. We show that conductin levels peak at G2/M followed by a rapid decline during return to G1. In line with this, Wnt/β-catenin target genes are low at G2/M and high at G1/S, and β-catenin phosphorylation oscillates during the cell cycle in a conductin-dependent manner. Conductin is degraded by the anaphase-promoting complex/cyclosome cofactor CDC20. Knockdown of CDC20 blocks Wnt signalling through conductin. CDC20-resistant conductin inhibits Wnt signalling and attenuates colony formation of colorectal cancer cells. We propose that CDC20-mediated degradation of conductin regulates Wnt/β-catenin signalling for maximal activity during G1/S.
Nikolaus-Fiebiger-Center of Molecular Medicine, University of Erlangen, Glueckstrasse 6, 91054 Erlangen, Germany.
Michel V
MV
Hadjihannas
Dominic B
DB
Bernkopf
Martina
M
Brückner
Jürgen
J
Behrens
D000595:Amino Acid Sequence; D000818:Animals; D060466:Axin Protein / Q000737:chemistry / Q000378:metabolism*; D064199:Cdc20 Proteins; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D051381:Rats; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
C491761:AXIN2 protein, human; D060466:Axin Protein; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D051176:beta Catenin; C577488:CDC20 protein, human; D046988:Proteasome Endopeptidase Complex