Regulation of the endothelial cell cycle by the ubiquitin-proteasome system.
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 beta-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.
Fasanaro
Pasquale
P
Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy.
Capogrossi
Maurizio C
MC
Martelli
Fabio
F
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology; D002453:Cell Cycle; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D044843:SKP Cullin F-Box Protein Ligases / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology*
D051267:NF-E2-Related Factor 2; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044843:SKP Cullin F-Box Protein Ligases; D046988:Proteasome Endopeptidase Complex