各种金属对铁调节蛋白-1的调节作用。

Modulation of iron regulatory protein-1 by various metals.

作者信息

Oshiro Satoru, Nozawa Koji, Hori Makoto, Zhang Chun, Hashimoto Yoshinori, Kitajima Shigetaka, Kawamura Ken-ichi

机构信息

Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

出版信息

Biochem Biophys Res Commun. 2002 Jan 11;290(1):213-8. doi: 10.1006/bbrc.2001.6182.

DOI:10.1006/bbrc.2001.6182

PMID:11779155

Abstract

Iron regulatory protein-1 (IRP-1) is known as a cytosolic aconitase and a central regulator of iron (Fe) homeostasis. IRP-1 regulates the expression of Fe metabolism-related proteins by interacting with the Fe-responsive element (IRE) in the untranslated regions of mRNAs of these proteins. However, it is less known whether IRP-1 modulates various non-Fe metals. In the present study, we showed that treatment of homogenously purified IRP-1 with non-Fe metals decreased the affinity to IRE in RNA band shift assays and increased aconitase activity. Non-Fe metals also inhibited (55)Fe incorporation into the fourth labile position of the Fe-S cluster of IRP-1. In PLC hepatoma cells, metal loading inactivated binding activity and activated enzyme activity. It also suppressed transferrin receptor mRNA expression in the cells. These results suggest that various non-Fe metals modulate IRP-1 by conversion of the 3Fe-4S apo-form to a [1 non-Fe metal + 3Fe]-4Fe holo-form.

摘要

铁调节蛋白-1（IRP-1）被认为是一种胞质乌头酸酶，是铁（Fe）稳态的核心调节因子。IRP-1通过与这些蛋白质mRNA非翻译区的铁反应元件（IRE）相互作用来调节铁代谢相关蛋白的表达。然而，IRP-1是否调节各种非铁金属尚不清楚。在本研究中，我们发现用非铁金属处理纯化的IRP-1会降低RNA凝胶迁移试验中其与IRE的亲和力，并增加乌头酸酶活性。非铁金属还抑制（55）Fe掺入IRP-1铁硫簇的第四个不稳定位置。在PLC肝癌细胞中，金属加载使结合活性失活并激活酶活性。它还抑制了细胞中转铁蛋白受体mRNA的表达。这些结果表明，各种非铁金属通过将3Fe-4S脱辅基形式转化为[1种非铁金属+3Fe]-4Fe全酶形式来调节IRP-1。