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Destabilization of AT 1 Receptor mRNA by Calreticulin

2002; Lippincott Williams & Wilkins; Volume: 90; Issue: 1 Linguagem: Inglês

10.1161/hh0102.102503

1524-4571

Georg Nickenig, Frank Michaelsen, Cornelius Müller, Anja Berger, Thomas Vogel, Agapios Sachinidis, H. Vetter, Michael Böhm,

Hormonal Regulation and Hypertension

AT 1 receptor activation leads to vasoconstriction, blood pressure increase, free radical release, and cell growth. AT 1 receptor regulation contributes to the adaptation of the renin-angiotensin system to long-term stimulation and serves as explanation for the involvement of the AT 1 receptor in the pathogenesis of cardiovascular disease. The molecular mechanisms involved in AT 1 receptor regulation are poorly understood. Here, we report that angiotensin II accelerates AT 1 receptor mRNA decay in vascular smooth muscle cells. A cognate mRNA region within the 3′ untranslated region at bases 2175 to 2195 governs the inducible decay of the AT 1 receptor mRNA. Sequential protein purifications led to the discovery of a novel mRNA binding protein, calreticulin, which mediates destabilization of the AT 1 receptor mRNA. Angiotensin II–caused phosphorylation of calreticulin enables binding of calreticulin to the AT 1 receptor mRNA at bases 2175 to 2195 and propagates calreticulin-induced acceleration of AT 1 receptor mRNA decay. Thus, a novel mRNA binding protein, calreticulin, is discovered, which causes AT 1 receptor mRNA degradation via binding to a distinct mRNA region in the 3′ untranslated region. These findings display a novel mechanism of posttranscriptional mRNA processing.