Figure 2.

Summary of the interactions between SIRT1 and the canonical Wnt pathway. In healthy homeostatic conditions SIRT1 binds to p300, diminishing its ability to acetylate the β-Catenin complex, comprised of Dvl, GSK3β and β-Catenin. Additionally, SIRT1 deacetylates both β-Catenin and HMGB1 thus inhibiting their translocation to the nucleus, inactivating Wnt signaling and stopping the development of vascular calcification. In the absence of SIRT1 the β-Catenin complex is activated by p300-mediated acetylation and GSK3β-catalyzed phosphorylation, inhibiting its ability to degrade β-Catenin. Additionally, HMGB1 and β-Catenin are also acetylated via p300, facilitating their translocation to the nucleus. Subsequently β-Catenin binds cofactors TCF/LEF and following their acetylation transcription of osteogenic factors Runx2 and BMPs is induced. Whilst the epigenetic roles of CBP and p300 are distinct, the role of CBP still remains an area for further investigation. LRP5/6, Low-density lipoprotein Receptor-related Protein 5/6; APC, Adenomatous Polyposis Coli; GSK3β, Glycogen Synthase Kinase-3 beta; Dvl, Dishelved Protein; TCF/LEF, T-Cell Factor/Lymphoid enhancer factor; Runx2, Runt-Related Transcription Factor; BMPs, Bone Morphogenic Proteins; HMGB1, High Mobility Group Box 1; ROS, Reactive Oxygen Species; Ac, Acetylation; P, Phosphorylation.