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Disturbed flow: p53 SUMOylation in the turnover of endothelial cells.

Takabe W, Alberts-Grill N, Jo H - J. Cell Biol. (2011)

Bottom Line: Cell Biol. doi:10.1083/jcb.201010051) sheds light on p53's role in this phenomenon.Disturbed flow induces peroxynitrite production, which activates protein kinase C ζ and it's binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy).This leads to p53 SUMOylation and its export to the cytosol, where it binds to the antiapoptotic protein Bcl-2 to induce apoptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30322, USA.

ABSTRACT
Disturbed blood flow induces apoptosis of vascular endothelial cells, which causes atherosclerosis. In this issue, Heo et al. (2011. J. Cell Biol. doi:10.1083/jcb.201010051) sheds light on p53's role in this phenomenon. Disturbed flow induces peroxynitrite production, which activates protein kinase C ζ and it's binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy). This leads to p53 SUMOylation and its export to the cytosol, where it binds to the antiapoptotic protein Bcl-2 to induce apoptosis.

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p53 coordinates the opposing effects of stable and disturbed blood flow on endothelial cell turnover. (A) A proposed pathway including a timeline by which disturbed flow is sensed by mechanosensors, which induces peroxynitrite (ONOO−) production, PKCζ phosphorylation, activation of E3 SUMO ligase PIASy, SUMOylation of p53, and its translocation to the cytosol, where it binds Bcl-2. Upon binding SUMOylated p53, Bcl-2 likely releases bax, which stimulates cytochrome c release from mitochondria, leading to apoptosome formation, caspase activation, and subsequent apoptosis. (B) Posttranslational modification of p53 (phosphorylation and SUMOylation under stable and disturbed flow, respectively) determines cell turnover and atherosclerosis. P, phosphorylation of p53.
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fig1: p53 coordinates the opposing effects of stable and disturbed blood flow on endothelial cell turnover. (A) A proposed pathway including a timeline by which disturbed flow is sensed by mechanosensors, which induces peroxynitrite (ONOO−) production, PKCζ phosphorylation, activation of E3 SUMO ligase PIASy, SUMOylation of p53, and its translocation to the cytosol, where it binds Bcl-2. Upon binding SUMOylated p53, Bcl-2 likely releases bax, which stimulates cytochrome c release from mitochondria, leading to apoptosome formation, caspase activation, and subsequent apoptosis. (B) Posttranslational modification of p53 (phosphorylation and SUMOylation under stable and disturbed flow, respectively) determines cell turnover and atherosclerosis. P, phosphorylation of p53.

Mentions: Endothelial cells contain numerous mechanosensors that detect local shear stress forces and transduce them into a variety of cell signaling pathways (Fig. 1 A). Via these mechanosensors, stable flow induces cell cycle arrest and inhibits apoptosis and inflammation in endothelial cells through acute and chronic mechanisms. Acute pathways include production of several factors, including nitric oxide (NO) from endothelial nitric oxide synthase (eNOS), which acts as a key mediator of the protective effect of stable flow. Long-term stable flow up-regulates atheroprotective genes, such as Klf2, eNOS, and antioxidant genes, coupled with the down-regulation of proinflammatory and proatherogenic genes (Ni et al., 2010).


Disturbed flow: p53 SUMOylation in the turnover of endothelial cells.

Takabe W, Alberts-Grill N, Jo H - J. Cell Biol. (2011)

p53 coordinates the opposing effects of stable and disturbed blood flow on endothelial cell turnover. (A) A proposed pathway including a timeline by which disturbed flow is sensed by mechanosensors, which induces peroxynitrite (ONOO−) production, PKCζ phosphorylation, activation of E3 SUMO ligase PIASy, SUMOylation of p53, and its translocation to the cytosol, where it binds Bcl-2. Upon binding SUMOylated p53, Bcl-2 likely releases bax, which stimulates cytochrome c release from mitochondria, leading to apoptosome formation, caspase activation, and subsequent apoptosis. (B) Posttranslational modification of p53 (phosphorylation and SUMOylation under stable and disturbed flow, respectively) determines cell turnover and atherosclerosis. P, phosphorylation of p53.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3105545&req=5

fig1: p53 coordinates the opposing effects of stable and disturbed blood flow on endothelial cell turnover. (A) A proposed pathway including a timeline by which disturbed flow is sensed by mechanosensors, which induces peroxynitrite (ONOO−) production, PKCζ phosphorylation, activation of E3 SUMO ligase PIASy, SUMOylation of p53, and its translocation to the cytosol, where it binds Bcl-2. Upon binding SUMOylated p53, Bcl-2 likely releases bax, which stimulates cytochrome c release from mitochondria, leading to apoptosome formation, caspase activation, and subsequent apoptosis. (B) Posttranslational modification of p53 (phosphorylation and SUMOylation under stable and disturbed flow, respectively) determines cell turnover and atherosclerosis. P, phosphorylation of p53.
Mentions: Endothelial cells contain numerous mechanosensors that detect local shear stress forces and transduce them into a variety of cell signaling pathways (Fig. 1 A). Via these mechanosensors, stable flow induces cell cycle arrest and inhibits apoptosis and inflammation in endothelial cells through acute and chronic mechanisms. Acute pathways include production of several factors, including nitric oxide (NO) from endothelial nitric oxide synthase (eNOS), which acts as a key mediator of the protective effect of stable flow. Long-term stable flow up-regulates atheroprotective genes, such as Klf2, eNOS, and antioxidant genes, coupled with the down-regulation of proinflammatory and proatherogenic genes (Ni et al., 2010).

Bottom Line: Cell Biol. doi:10.1083/jcb.201010051) sheds light on p53's role in this phenomenon.Disturbed flow induces peroxynitrite production, which activates protein kinase C ζ and it's binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy).This leads to p53 SUMOylation and its export to the cytosol, where it binds to the antiapoptotic protein Bcl-2 to induce apoptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30322, USA.

ABSTRACT
Disturbed blood flow induces apoptosis of vascular endothelial cells, which causes atherosclerosis. In this issue, Heo et al. (2011. J. Cell Biol. doi:10.1083/jcb.201010051) sheds light on p53's role in this phenomenon. Disturbed flow induces peroxynitrite production, which activates protein kinase C ζ and it's binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy). This leads to p53 SUMOylation and its export to the cytosol, where it binds to the antiapoptotic protein Bcl-2 to induce apoptosis.

Show MeSH
Related in: MedlinePlus