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

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Abstract

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.

Original languageEnglish
Pages (from-to)272-280
Number of pages9
JournalCardiovascular Research
Volume85
Issue number2
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Cell cycle
  • Endothelium
  • Oxidative stress
  • Proteasome
  • Ubiquitin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

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