[Frontiers in Bioscience 16, 1517-1535, January 1, 2011]

Proliferation unleashed: The role of Skp2 in vascular smooth muscle cell proliferation

Mark Bond1, Yih-Jer Wu2

1The Bristol Heart Institute, University of Bristol, Bristol, BS2 8HW, U.K., 2Department of Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, and the Department of Medicine, Mackay Medical College, and Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. p27Kip1 puts the brake on proliferation
4. Skp2 promotes p27Kip1 ubiquitination and degradation
5. The SCFSkp2 ubiquitin ligase
6. Skp2 targets multiple proteins for degradation
7. Skp2 controls VMSC proliferation and neointima formation
8. Multiple pathways regulate Skp2 expression
8.1. Skp2 protein stability
8.2. Growth Factors
8.3. Cyclic nucleotides
8.4. The Extracellular Matrix
8.5. Transcriptional regulation
9. SCFSkp2 as a drug target in cardiovascular disease
10. Acknowledgments
11. References

1. ABSTRACT

Vascular smooth muscle cell proliferation plays a major role in the development of numerous vascular pathologies. Understanding the molecular mechanisms that regulate smooth muscle cell proliferation is therefore essential for the development of new therapies for the treatment of these pathologies. Skp2 is an F-box protein component of the SCFSkp2 ubiquitin-ligase that controls cellular proliferation by regulating the ubiquitination and degradation of several cell-cycle regulatory proteins, including the cyclin-dependent kinase inhibitor, p27Kip1. This review discusses the recent literature on the function and regulation of Skp2 in smooth muscle cells, which is emerging as a key player in the control of smooth muscle cell proliferation during vascular disease.