The heterogenous nuclear riboprotein S1-1 regulates AT1 receptor gene expression via transcriptional and posttranscriptional mechanisms

被引:21
作者
Mueller, Cornelius F. H. [1 ]
Berger, Anja [2 ]
Zimmer, Sebastian [1 ]
Tiyerili, Vedat [1 ]
Nickenig, Georg [1 ]
机构
[1] Univ Klinikum Bonn, Med Klin & Poliklin 2, D-53105 Bonn, Germany
[2] Univ Klinikum Saarlandes, Klin & Poliklin Innere Med 3, D-66421 Homburg, Germany
关键词
S1-1; protein; VSMC; Angiotensin II; Apoptosis; Proliferation; Regulation; mRNA; Transfection; Transcriptional regulation; mRNA stability; MESSENGER-RNA; ANGIOTENSIN-II; HNRNP D; PROTEINS; DESTABILIZATION; IDENTIFICATION;
D O I
10.1016/j.abb.2009.06.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The AT1 receptor plays an essential role in the pathogenesis of atherosclerosis. AT1 receptor expression is predominately mediated via mRNA destabilization by mRNA binding proteins. We identified via MALDI-analysis the heterogenous nuclear riboprotein S1-1 as an important regulator of AT1 receptor mRNA stability. The S1-1 protein possesses multiple nucleolar and cellular functions in vascular smooth muscle cells (VSMC). Overexpression of S1-1 sense resulted in VSMC in significant stabilization of AT1 receptor mRNA. However, this stabilization of the AT1 receptor mRNA is accompanied by a significantly reduced AT1 receptor mRNA transcription as shown via nuclear run-on assay resulting finally in reduced AT1 receptor mRNA levels. Additionally, S1-1 overexpression leads to increased apoptosis in VSMC and decreases VSMC proliferation. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:76 / 82
页数:7
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