Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-: Therapeutic Implications for Cardiovascular Diseases
Figure 2
PPAR
targets cell-cycle progression. Phosphorylation of the retinoblastoma gene
product (pRB) by specific G1 CDKs represents the critical checkpoint
of the G1/S transition of the cell cycle. pRB phosphorylation
releases E2F allowing the expression of genes required for DNA synthesis. By
preventing the degradation of the CDK inhibitor (CDKI) p2, PPAR
ligands inhibit mitogen-induced pRB phosphorylation and downstream expression
of key E2F-regulated genes (i.e., MCM genes) responsible for the initiation of DNA replication.
