Modulation of iron regulatory protein-1 by various metals

被引：27

作者：

Oshiro, S

Nozawa, K

Hori, M

Zhang, C

Hashimoto, Y

Kitajima, S

Kawamura, K

机构：

[1] Tokyo Med & Dent Univ, Med Res Inst, Dept Biochem Genet, Bunkyo Ku, Tokyo 1138510, Japan

[2] Showa Coll Pharmaceut Sci, Dept Biochem, Tokyo 1940042, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2002年 / 290卷 / 01期

关键词：

iron regulatory protein-1; aconitase; iron-responsive element; iron; non-iron metals; essential metals; transition metals; heavy metals; transferrin receptor;

D O I：

10.1006/bbrc.2001.6182

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：

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 Fe-55 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. (C) 2002 Elsevier Science.

引用

页码：213 / 218

页数：6

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