| Autor: |
Santiago FS; Centre for Vascular Research, Department of Pathology, University of New South Wales, and Department of Haematology, The Prince of Wales Hospital, Sydney, NSW, Australia., Ishii H, Shafi S, Khurana R, Kanellakis P, Bhindi R, Ramirez MJ, Bobik A, Martin JF, Chesterman CN, Zachary IC, Khachigian LM |
| Jazyk: |
angličtina |
| Zdroj: |
Circulation research [Circ Res] 2007 Jul 20; Vol. 101 (2), pp. 146-55. Date of Electronic Publication: 2007 Jun 07. |
| DOI: |
10.1161/CIRCRESAHA.106.145235 |
| Abstrakt: |
Vascular injury initiates a cascade of phenotype-altering molecular events. Transcription factor function in this process, particularly that of negative regulators, is poorly understood. We demonstrate here that the forced expression of the injury-inducible GLI-Krüppel zinc finger protein Yin Yang-1 (YY1) inhibits neointima formation in human, rabbit and rat blood vessels. YY1 inhibits p21(WAF1/Cip1) transcription, prevents assembly of a p21(WAF1/Cip1)-cdk4-cyclin D1 complex, and blocks downstream pRb(Ser249/Thr252) phosphorylation and expression of PCNA and TK-1. Conversely, suppression of endogenous YY1 elevates levels of p21(WAF1/Cip1), PCNA, pRb(Ser249/Thr252) and TK-1, and increases intimal thickening. YY1 binds Sp1 and prevents its occupancy of a distinct element in the p21(WAF1/Cip1) promoter without YY1 itself binding the promoter. Additionally, YY1 induces ubiquitination and proteasome-dependent degradation of p53, decreasing p53 immunoreactivity in the artery wall. These findings define a new role for YY1 as both an inducer of p53 instability in smooth muscle cells, and an indirect repressor of p21(WAF1/Cip1) transcription, p21(WAF1/Cip1)-cdk4-cyclin D1 assembly and intimal thickening. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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