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Comment
. 2011 May 30;193(5):805-7.
doi: 10.1083/jcb.201104140.

Disturbed flow: p53 SUMOylation in the turnover of endothelial cells

Wakako Takabe  1 , Noah Alberts-Grill, Hanjoong Jo
Affiliations
Comment

Disturbed flow: p53 SUMOylation in the turnover of endothelial cells

Wakako Takabe et al. J Cell Biol. .

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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Figures

Figure 1.
Figure 1.
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.
See this image and copyright information in PMC

Comment on

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