Antimitogenic effects of prostacyclin on the G1 phase cyclin-dependent kinases.
The prostanoid prostacyclin (PGI2) inhibits proliferation of cultured vascular SMCs by inhibiting cell cycle progression from G1 to S phase. Progression through G1 phase is regulated by the sequential activation of the G1 phase cyclin-dependent kinases (cdks). Recent studies have shown that PGI2-dependent activation of its receptor, IP, inhibits G1 phase progression by blocking the degradation of p27 and the activation of cyclin E-cdk2. High Density Lipoproteins (HDL) and its associated apolipoprotein, ApoE, also inhibit S phase entry of vascular SMCs, and the effects of HDL and ApoE are, at least in part, also mediated by the production of PGI2. The antimitogenic effects of hyaluronan may also be controlled by PGI2. This review summarizes the effects of PGI2 on the G1 phase cyclin-cdks and discusses the potential role of PGI2 as a common component of multiple extracellular signals that attenuate the proliferation of vascular SMCs.
Kothapalli
Devashish
D
Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 167 Johnson Pavilion, Philadelphia, PA 19104-6084, USA.
Flores-Stewart
Sheryl A
SA
Assoian
Richard K
RK
D019925:Cyclin A / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D016193:G1 Phase; D006801:Humans; D018960:Hyaluronan Receptors / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000494:pharmacology; D008934:Mitogens / Q000037:antagonists & inhibitors*; D008938:Mitosis / Q000187:drug effects*; D010766:Phosphorylation; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics
D019925:Cyclin A; D004967:Estrogens; D018960:Hyaluronan Receptors; D008934:Mitogens; D044786:S-Phase Kinase-Associated Proteins; D006820:Hyaluronic Acid; D018844:Cyclin-Dependent Kinases