β-Catenin C-terminal signals suppress p53 and are essential for artery formation

Dario F. Riascos-Bernal, Prameladevi Chinnasamy, Longyue Cao, Charlene M. Dunaway, Tomas Valenta, Konrad Basler, Nicholas E.S. Sibinga

Research output: Contribution to journalArticle

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Abstract

Increased activity of the tumour suppressor p53 is incompatible with embryogenesis, but how p53 is controlled is not fully understood. Differential requirements for p53 inhibitors Mdm2 and Mdm4 during development suggest that these control mechanisms are context-dependent. Artery formation requires investment of nascent endothelial tubes by smooth muscle cells (SMCs). Here, we find that embryos lacking SMC β-catenin suffer impaired arterial maturation and die by E12.5, with increased vascular wall p53 activity. β-Catenin-deficient SMCs show no change in p53 levels, but greater p53 acetylation and activity, plus impaired growth and survival. In vivo, SMC p53 inactivation suppresses phenotypes caused by loss of β-catenin. Mechanistically, β-catenin C-terminal interactions inhibit Creb-binding protein-dependent p53 acetylation and p53 transcriptional activity, and are required for artery formation. Thus in SMCs, the β-catenin C-terminus indirectly represses p53, and this function is essential for embryogenesis. These findings have implications for angiogenesis, tissue engineering and vascular disease.

Original languageEnglish (US)
Article number12389
JournalNature Communications
Volume7
DOIs
StatePublished - Aug 8 2016

Fingerprint

smooth muscle
Catenins
muscle cells
arteries
Smooth Muscle Myocytes
Muscle
Arteries
acetylation
Acetylation
Embryonic Development
suppressors
angiogenesis
phenotype
tissue engineering
embryos
Tissue Engineering
Vascular Diseases
Tissue engineering
deactivation
inhibitors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Riascos-Bernal, D. F., Chinnasamy, P., Cao, L., Dunaway, C. M., Valenta, T., Basler, K., & Sibinga, N. E. S. (2016). β-Catenin C-terminal signals suppress p53 and are essential for artery formation. Nature Communications, 7, [12389]. https://doi.org/10.1038/ncomms12389

β-Catenin C-terminal signals suppress p53 and are essential for artery formation. / Riascos-Bernal, Dario F.; Chinnasamy, Prameladevi; Cao, Longyue; Dunaway, Charlene M.; Valenta, Tomas; Basler, Konrad; Sibinga, Nicholas E.S.

In: Nature Communications, Vol. 7, 12389, 08.08.2016.

Research output: Contribution to journalArticle

Riascos-Bernal, DF, Chinnasamy, P, Cao, L, Dunaway, CM, Valenta, T, Basler, K & Sibinga, NES 2016, 'β-Catenin C-terminal signals suppress p53 and are essential for artery formation', Nature Communications, vol. 7, 12389. https://doi.org/10.1038/ncomms12389
Riascos-Bernal DF, Chinnasamy P, Cao L, Dunaway CM, Valenta T, Basler K et al. β-Catenin C-terminal signals suppress p53 and are essential for artery formation. Nature Communications. 2016 Aug 8;7. 12389. https://doi.org/10.1038/ncomms12389
Riascos-Bernal, Dario F. ; Chinnasamy, Prameladevi ; Cao, Longyue ; Dunaway, Charlene M. ; Valenta, Tomas ; Basler, Konrad ; Sibinga, Nicholas E.S. / β-Catenin C-terminal signals suppress p53 and are essential for artery formation. In: Nature Communications. 2016 ; Vol. 7.
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