Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondria protein with an N-terminal mitochondrial targeting sequence and induces apoptosis.
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.
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Lab of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, 38# Xueyuan Road, Beijing, 100083, PR China.
Yu
C F
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Chen
Y Y
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Lu
Y
Y
Guo
J H
JH
Song
Q S
QS
Ma
D L
DL
Shi
T P
TP
Wang
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L
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D003001:Cloning, Molecular; D019295:Computational Biology; D045304:Cytochromes c / Q000378:metabolism; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification* / Q000502:physiology*; D008969:Molecular Sequence Data; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification* / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D024101:Mitochondrial Proteins; D021382:Protein Sorting Signals; D045304:Cytochromes c; D017027:Protein Tyrosine Phosphatases; C515449:RMDN3 protein, human