凋亡相关蛋白3，一种全反式维甲酸上调的膜蛋白，通过降低细胞周期蛋白D1的表达将细胞周期阻滞在G1/S期。

Apoptosis related protein 3, an ATRA-upregulated membrane protein arrests the cell cycle at G1/S phase by decreasing the expression of cyclin D1.

作者信息

Yu Fang, Yang Guodong, Zhao Zhongliang, Ji Lin, Cao Yunxin, Bai Liyuan, Lu Fan, Fu Haiyan, Huang Bo, Li Hua, Zhang Jie, Yao Libo, Lu Zifan

机构信息

Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an 710032, PR China.

出版信息

Biochem Biophys Res Commun. 2007 Jul 13;358(4):1041-6. doi: 10.1016/j.bbrc.2007.05.049. Epub 2007 May 14.

DOI:10.1016/j.bbrc.2007.05.049

Abstract

Human Apr3 was first cloned from HL-60 cells treated by ATRA. In this study, we further demonstrated that Apr3 could be obviously upregulated by ATRA in many other ATRA sensitive cells, suggesting a common role of Apr3 in ATRA effects. Indirect immunofluorescence assay indicates that Apr3 is a membrane protein, while its truncated form without the predicted transmembrane and intracellular domain, was likely a secreted one. Furthermore, FACS analysis showed that Apr3 overexpression could cause an obvious G1/S phase arrest which might be induced by dramatic reduction of cyclin D1 expression. Strikingly, the truncated Apr3 antagonized the negative role of Apr3 on cell cycle and cyclin D1. Taken together, our data suggest that Apr3 should play an important role in ATRA signal pathway and the predicted transmembrane and/or the intracellular domain mediates Apr3 membrane localization and is vital for the negative regulation on cell cycle and cyclin D1.

摘要

人Apr3最初是从经全反式维甲酸（ATRA）处理的HL-60细胞中克隆得到的。在本研究中，我们进一步证明，Apr3在许多其他对ATRA敏感的细胞中可被ATRA显著上调，提示Apr3在ATRA作用中具有共同作用。间接免疫荧光分析表明Apr3是一种膜蛋白，而其没有预测的跨膜和胞内结构域的截短形式可能是一种分泌蛋白。此外，流式细胞术分析显示Apr3过表达可导致明显的G1/S期阻滞，这可能是由细胞周期蛋白D1表达显著降低所诱导的。引人注目的是，截短的Apr3拮抗Apr3对细胞周期和细胞周期蛋白D1的负面作用。综上所述，我们的数据表明Apr3在ATRA信号通路中应发挥重要作用，并且预测的跨膜和/或胞内结构域介导Apr3的膜定位，对细胞周期和细胞周期蛋白D1的负调控至关重要。