Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondria protein with an N-terminal mitochondrial targeting sequence and induces apoptosis

Abstract

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.

Expression of the novel protein PTPIP51 in rat liver: an immunohistochemical study

“…Since the mitochondrial target sequence described by Lv et al (2006) is located at the N-terminus of PTPIP51, isoforms of PTPIP51 lacking the N-terminus and the target sequence would not be able to bind to mitochondria. This hypothesis is corroborated by the fact that a GFP-labelled PTPIP51 lacking the N-terminal 30 amino acids PTPIP51 was exclusively localized in the cytosol when expressed in HEK293 cells (D. Schreiner, unpublished results).…”

Expression of PTPIP51 during mouse eye development

“…Based on the study conducted by Lv et al (2006), one can hypothesize a potential regulating part for PTPIP51 in retinal apoptotic processes. The role of apoptosis in remodelling processes of the retina until day P14 is a well established mechanism (Smith et al 2002;Linden et al 2005;Marigo 2007).…”

“…The role of apoptosis in remodelling processes of the retina until day P14 is a well established mechanism (Smith et al 2002;Linden et al 2005;Marigo 2007). It is important, however, that only overexpression of the full-length protein harboring a mitochondrial targeting sequence is capable of inducing apoptosis (Lv et al 2006). PTPIP51 lacking this N-terminal sequence shows a cytosolic localization and is unable to induce programmed cell death.…”

Protein Tyrosine Phosphatase Interacting Protein 51 (PTPIP51) mRNA Expression and Localization and Its In Vitro Interacting Partner Protein Tyrosine Phosphatase 1B (PTP1B) in Human Placenta of the First, Second, and Third Trimester

“…The human Ptpip51 gene is located on chromosome 15 (15q15.1) and encodes the corresponding full-length protein making up 470 amino acids by 12 exons. PTPIP51 is evolutionary conserved and was shown to be expressed in different mammalian tissues and organs (Stenzinger et al 2005), cancer (Lv et al 2006;Koch et al in press), as well as different cell lines including BeWo cells (human choriocarcinoma cell line) (Stenzinger et al 2005). A regulated layer-dependent expression pattern was particularly observed for epidermal and seminiferous epithelia, both requiring a carefully controlled balance between proliferation, dif-ferentiation, and apoptosis (Nickoloff and Denning 2001;Stenzinger et al 2005Stenzinger et al ,2006.…”