title: Identification of a novel cell-penetrating peptide from human phosphatidate phosphatase LPIN3.
abstract: Biomolecules such as proteins, DNA, and RNA are macromolecules and can not cross the cell membrane. However, cell-penetrating peptide (CPP) has been shown to deliver therapeutic biomolecules successfully into cells. The various and widely used CPPs including TAT, VP22, and Antp are mostly non-human originated CPPs, and are limited by their potential toxicity and immunogenicity. We report here on a newly identified novel cell-penetrating sequence (LPIN; RRKRRRRRK) from the nuclear localization sequence (NLS) of human nuclear phosphatase, LPIN3. LPIN-EGFP recombinant protein was concentration- and time-dependently delivered into cells and localized to the nucleus as well as the cytoplasm. It penetrated the cell membrane by lipid raft-mediated endocytosis by binding to heparan sulfate proteoglycan. LPIN-EGFP was successfully delivered into primary mouse splenocytes in vitro and it could be delivered into various tissues including liver, kidney, and intestine in mice after intra-peritoneal injection. This research suggests that LPIN-CPP could be used in a drug delivery system to deliver therapeutic biomolecules including peptides, proteins, DNA, and RNA and without the limitations of non-human originated CPPs such as TAT-CPP.
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Korea.
authors.forename: Sangho
authors.initials: S
authors.lastname: Lim
authors.forename: Won-ju
authors.initials: WJ
authors.lastname: Kim
authors.forename: Yeon-ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Je-Min
authors.initials: JM
authors.lastname: Choi
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008969:Molecular Sequence Data; D010711:Phosphatidate Phosphatase / Q000235:genetics* / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; C584419:LPIN3 protein, human; D010711:Phosphatidate Phosphatase