Identification and characterization of a novel protein ISOC2 that interacts with p16INK4a
Identification and characterization of a novel protein ISOC2 that interacts with p16INK4a
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与 p16INK4a 相互作用的新型蛋白质 ISOC2 的鉴定和表征。
DOI：
10.1016/j.bbrc.2007.06.181
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发表时间：
2007-09-21
影响因子：
3.1
通讯作者：
Fu, Songbin
中科院分区：
文献类型：
--
作者：
Huang, Xiaoyi;Shi, Zhongcheng;Fu, Songbin
p16（INK4a）是一种多肿瘤抑制因子，在肿瘤的增殖和发生中起重要作用。为了筛选p16（INK4a）相关蛋白，我们进行了酵母双杂交试验，并确定了一个新的蛋白质isochorismatase域包含2（ISOC 2）。ISOC 2在不同物种中保守，在人和小鼠中分别编码205和210个氨基酸。ISOC 2在小鼠中的表达是普遍的，但主要在子宫、胃和泌尿道系统中表达。ISOC 2和p16（INK4a）之间的相互作用进行了验证，在体外下拉测定和体内免疫共沉淀。使用绿色和青色荧光融合蛋白的共聚焦显微镜研究确定ISOC 2与p16（INK 4a）共定位。过表达的ISOC 2能够以剂量依赖性方式抑制p16（INK4a）。我们的数据表明，ISOC 2是一种新的功能蛋白，它能够与肿瘤抑制基因INK4，INK4，p16（INK4a）结合并共定位。过表达的ISOC 2抑制p16（INK4a）的表达，表明该新基因可能通过与p16（INK4a）相互作用在INK4a肿瘤发展过程中发挥作用。(c)2007爱思唯尔公司All rights reserved.
p16(INK4a), is a multiple tumor suppressor, playing an important role in proliferation and tumorigenesis. To screen the p16(INK4a) -associated proteins, we performed a yeast two-hybrid assay and identified a novel protein isochorismatase domain containing 2 (ISOC2). ISOC2 conserves in different species, and encodes 205 and 210 amino acids in human and mouse, respectively. The expression of ISOC2 in mouse is universal but predominantly in uterus, stomach, and urinary tract system. Interaction between ISOC2 and p16(INK4a) was verified using in vitro pull-down assays and in vivo co-immunoprecipitation. Confocal microscopy studies using green and cyan fluorescent fusion proteins determined that ISOC2 co-localizes with p16(INK4a). Over-expressed ISOC2 is able to inhibit p16(INK4a) in dose-dependent manner. Our data indicated that ISOC2 is a novel functional protein, which is able to bind and co-localize with a tumor suppressor INK4, INK4, gene p16(INK4a). Over-expressed ISOC2 inhibits the expression of p16(INK4a), suggesting that this novel gene may play a role during the INK4a tumor development by interacting with p16(INK4a). (c) 2007 Elsevier Inc. All rights reserved.