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Cardiovascular Research Advance Access first published online on July 17, 2009
This version [Corrected Proof] published online on August 7, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp244
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Regulation of the endothelial cell cycle by the ubiquitin–proteasome system

Pasquale Fasanaro, Maurizio C. Capogrossi and Fabio Martelli*

Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy

* Corresponding author. Tel: +39 06 6646 2431/33/34, Fax: +39 06 6646 2430, Email: f.martelli{at}idi.it

Degradation of poly-ubiquitinated proteins by the 26S-proteasome complex represents a crucial quantitative control mechanism. The ubiquitin–proteasome system (UPS) plays a pivotal role in the complex molecular network regulating the progression both between and within each cell-cycle phase. Two major complexes are involved: the SKP1-CUL1-F-box-protein complex (SCF) and the anaphase-promoting complex/cyclosome (APC/C). Notwithstanding structural similarities, SCF and APC/C display different cellular functions and mechanisms of action. SCF modulates all cell-cycle stages and plays a prominent role at G1/S transition mainly through three regulatory subunits: Skp2, Fbw7, and β-TRCP. APC/C, regulated by Cdc20 or Cdh1 subunits, has a crucial role in mitosis. In this review, we will describe how the endothelial cell cycle is regulated by the UPS. We will illustrate the principal SCF- and APC/C-dependent molecular mechanisms that modulate cell growth, allowing a unidirectional cell-cycle progression. Then, we will focus our attention on UPS modulation by oxidative stress, a pathogenic stimulus that causes endothelial dysfunction and is involved in numerous cardiovascular diseases.

KEYWORDS Cell cycle; Endothelium; Oxidative stress; Proteasome; Ubiquitin

Time for primary review: 30 days

This article is part of the Spotlight Issue on: The Role of the Ubiquitin-Proteasome Pathway in Cardiovascular Disease


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