Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondria protein with an N-terminal mitochondrial targeting sequence and induces apoptosis
Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondria protein with an N-terminal mitochondrial targeting sequence and induces apoptosis
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DOI：
10.1007/s10495-006-8882-9
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发表时间：
2006-09-01
期刊：
影响因子：
7.2
通讯作者：
Wang, L.
中科院分区：
文献类型：
--
作者：
Lv, B. F.;Yu, C. F.;Wang, L.
细胞凋亡是由基因决定的细胞自杀程序。线粒体在这一过程中起着核心作用，并且已经显示出各种分子调节该细胞器中的细胞凋亡。本研究首次发现蛋白酪氨酸磷酸酶相互作用蛋白51（PTPIP 51）是一种新的线粒体蛋白，可诱导HEK 293 T和HeLa细胞凋亡。PTPIP 51转染导致磷脂酰丝氨酸（PS）的外化，caspase-3的激活，PARP的切割和核DNA的缩合。进一步的研究表明PTPIP 51过表达导致线粒体膜电位降低和细胞色素c的释放，表明其可能参与线粒体/细胞色素c介导的凋亡途径。我们还发现，PTPIP 51的N末端附近的一个假定的TM结构域是其靶向线粒体所必需的，这一发现证明了PTPIP 51 TM结构域的缺失阻止了蛋白质的线粒体定位。此外，该缺失显著影响PTPIP 51诱导细胞凋亡的能力。总之，本研究的结果表明，PTPIP 51是一种线粒体蛋白，具有凋亡诱导功能，并且N-末端TM结构域是蛋白质正确靶向线粒体及其凋亡功能所必需的。
Apoptosis is a genetically determined cell suicide program. Mitochondria play a central role in this process and various molecules have been shown to regulate apoptosis in this organelle. In the present study, we firstly identified that protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondrial protein, which may induce apoptosis in HEK293T and HeLa cell lines. PTPIP51 transfection resulted in the externalization of phosphatidylserine (PS), activation of caspase-3, cleavage of PARP, and condensation of nuclear DNA. Further investigation revealed that PTPIP51 over-expression caused a decrease in mitochondrial membrane potential and release of cytochrome c, suggesting that it may be involved in a mitochondria/cytochrome c mediated apoptosis pathway. We also found that a putative TM domain near the N terminus of PTPIP51 is required for its targeting to mitochondria, as evidenced by the finding that deletion of the PTPIP51 TM domain prevented the protein's mitochondiral localization. Furthermore, this deletion significantly influenced the ability of PTPIP51 to induce apoptosis. Taken together, the results of the present study suggest that PTPIP51 is a mitochondrial protein with apoptosis-inducing function and that the N-terminal TM domain is required for both the correct targeting of the protein to mitochondria and its apoptotic functions.