Song Hai, Li Yiliang, Chen Guoyuan, Xing Zhen, Zhao Jing, Yokoyama Kazunari K, Li Tsaiping, Zhao Mujun
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Biochem Biophys Res Commun. 2004 Apr 16;316(4):1116-23. doi: 10.1016/j.bbrc.2004.02.166.
Human LPTS/PinX1 is a telomerase-inhibitory protein, which binds to the telomere protein Pin2/TRF1 and the catalytic subunit hTERT of telomerase. To explore the proteins that might be involved in the telomerase pathway, we performed a yeast two-hybrid screening with LPTS/PinX1 as the bait. A novel gene, MCRS2, encoding for an isoform of MCRS1/p78 and MSP58 was isolated. The expression of MCRS2 protein is cell-cycle dependent, accumulating in the very early S phase. MCRS2 interacts with LPTS/PinX1 in vitro, in vivo and colocalizes with LPTS/PinX1 in cells. MCRS2 and its amino terminus inhibit telomerase activity in vitro and long-term overexpression of MCRS2 in SMMC-7721 cells results in a gradual and progressive shortening of telomeres. Our findings suggest that MCRS2 might be a linker between telomere maintenance and cell-cycle regulation.
人LPTS/PinX1是一种端粒酶抑制蛋白，它与端粒蛋白Pin2/TRF1以及端粒酶的催化亚基hTERT相结合。为了探索可能参与端粒酶途径的蛋白质，我们以LPTS/PinX1作为诱饵进行了酵母双杂交筛选。分离出了一个新基因MCRS2，它编码MCRS1/p78和MSP58的一种异构体。MCRS2蛋白的表达依赖于细胞周期，在S期早期积累。MCRS2在体外、体内均与LPTS/PinX1相互作用，并在细胞中与LPTS/PinX1共定位。MCRS2及其氨基末端在体外抑制端粒酶活性，在SMMC-7721细胞中长期过表达MCRS2会导致端粒逐渐且持续缩短。我们的研究结果表明，MCRS2可能是端粒维持与细胞周期调控之间的一个连接分子。
