Apoptosis related protein 3 is a lysosomal membrane protein
Apoptosis related protein 3 is a lysosomal membrane protein
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DOI：
10.1016/j.bbrc.2015.03.127
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发表时间：
2015-05-15
影响因子：
3.1
通讯作者：
Zhang, HuiWen
中科院分区：
文献类型：
--
作者：
Ding, XiaoDong;Chen, YuanWen;Zhang, HuiWen
凋亡相关蛋白3（Apoptosis Related Protein 3，APR 3）是一种重要的蛋白质，参与维甲酸诱导的细胞凋亡、成骨细胞分化及宫颈鳞癌的发生发展。虽然它被预测为跨膜蛋白，但其细胞定位尚不清楚。本研究利用生物信息学工具对APR 3进行分析，发现APR 3含有一个潜在的信号肽、一个跨膜区和3个N-糖基化位点，这些都是溶酶体蛋白的特征。Western blot结果显示，APR 3主要存在于溶酶体中，尤其是溶酶体膜部分，而不在内质网中。同时，双重免疫荧光证实，APR 3与溶酶体膜蛋白，LAMP 1，以及溶酶体特异性标志物，Lyso-Tracker Red共定位。此外，我们还发现，APR 3在肺、肝、脾、肾和脂肪组织中高表达，而在心脏、胰腺、胃和肠中表达水平较低。有趣的是，与正常肝细胞相比，APR 3表达在多种肝细胞癌细胞系中升高。总之，我们的研究结果证明了APR 3是一种新的溶酶体膜蛋白，并阐明了其可能的功能。(C)2015 Elsevier Inc. All rights reserved.
Apoptosis Related Protein 3 (APR3) is an important protein which is involved in retinoic acid-induced apoptosis, osteoblast differentiation and cervical squamous cell carcinoma progression. Although it was predicted to be a trans-membrane protein, its cellular localization is not clear. In this study, we analyzed APR3 with bioinformatic tools and found that APR3 contains a potential signal peptide, a transmembrane region and 3 N-glycosylation sites, all of which are characteristics of lysosomal proteins. Western blot with isolated lysosomes demonstrated that APR3 was mainly present in lysosomes, specially in the lysosomal membrane fraction, but not in endoplasmic reticulum. Concomitantly, double immunofluorescence confirmed that APR3 co-localized with lysosomal membrane protein, LAMP1, as well as lysosomal specific marker, Lyso-Tracker Red. Moreover, we showed that APR3 was highly expressed in the lung, liver, spleen, kidney and adipose tissue, but expressed at the low level in the heart, pancreas, stomach and intestine. Interestingly, APR3 expression was elevated in multiple hepatocellular carcinoma cell lines comparing to normal liver cells. Collectively, our results proved that APR3 is a novel lysosomal membrane protein and shed light on its possible functions. (C) 2015 Elsevier Inc. All rights reserved.