Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3

被引：602

作者：

Lin, BZ ^{[1
]}

Kolluri, SK ^{[1
]}

Lin, F ^{[1
]}

Liu, W ^{[1
]}

Han, YH ^{[1
]}

Cao, XH ^{[1
]}

Dawson, MI ^{[1
]}

Reed, JC ^{[1
]}

Zhang, XK ^{[1
]}

机构：

[1] Burnham Inst, Ctr Canc, La Jolla, CA 92037 USA

来源：

CELL | 2004年 / 116卷 / 04期

关键词：

D O I：

10.1016/S0092-8674(04)00162-X

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 Bcl-2 family proteins are key regulators of apoptosis in human diseases and cancers. Though known to block apoptosis, Bcl-2 promotes cell death through an undefined mechanism. Here, we show that Bcl-2 interacts with orphan nuclear receptor Nur77 (also known as TR3), which is required for cancer cell apoptosis induced by many antineoplastic agents. The interaction is mediated by the N-terminal loop region of Bcl-2 and is required for Nur77 mitochondrial localization and apoptosis. Nur77 binding induces a Bcl-2 conformational change that exposes its BH3 domain, resulting in conversion of Bcl-2 from a protector to a killer. These findings establish the coupling of Nur77 nuclear receptor with the Bcl-2 apoptotic machinery and demonstrate that Bcl-2 can manifest opposing phenotypes, induced by interactions with proteins such as Nur77, suggesting novel strategies for regulating apoptosis in cancer and other diseases.

引用

收藏

页码：527 / 540

页数：14

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