Yin Yang-1 Inhibits Vascular Smooth Muscle Cell Growth and Intimal Thickening by Repressing p21 WAF1/Cip1 Transcription and p21 WAF1/Cip1 -Cdk4-Cyclin D1 Assembly

• DOI: 10.1161/circresaha.106.145235
• Publication Date: 2007-06-08T01:11:22Z
• Authors: Fernando S. Santiago; Hideto Ishii; Shahida Shafi; Rohit Khurana; Peter Kanellakis; Ravinay Bhindi; Manfred J. Ramirez; Alexander Bobik; John F. Martin; Colin N. Chesterman; Ian C. Zachary; Levon M. Khachigian
• Keywords: Transcription

Vascular injury initiates a cascade of phenotype-altering molecular events. Transcription factor function in this process, particularly that negative regulators, is poorly understood. We demonstrate here the forced expression injury-inducible GLI-Krüppel zinc finger protein Yin Yang-1 (YY1) inhibits neointima formation human, rabbit and rat blood vessels. YY1 p21 WAF1/Cip1 transcription, prevents assembly -cdk4-cyclin D1 complex, blocks downstream pRb Ser249/Thr252 phosphorylation PCNA TK-1. Conversely, suppression endogenous elevates levels , PCNA, TK-1, increases intimal thickening. binds Sp1 its occupancy distinct element promoter without itself binding promoter. Additionally, induces ubiquitination proteasome-dependent degradation p53, decreasing p53 immunoreactivity artery wall. These findings define new role for as both an inducer instability smooth muscle cells, indirect repressor