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| Content Provider | Springer Nature Link |
|---|---|
| Author | Koo, Ja Hyun Yoon, Heeseok Kim, Won Ju Lim, Sangho Park, Hong Jai Choi, Je Min |
| Copyright Year | 2014 |
| Abstract | Cytokines are released from the cell, bind to their receptors, and affect cellular responses. The precursor form of interleukin 1 alpha (pIL-1α) has a nuclear localization sequence (NLS) that causes it to be localized to the nucleus and regulate specific gene expression. The amino acids of the NLS are basic amino acid-rich sequences, as is the cell penetrating peptide (CPP), which has been widely studied as a way to deliver macromolecules into cells. Here, we hypothesized that the NLS in pIL-1α (pIL-1αNLS) can penetrate the cell membrane and it could deliver macromolecules such as protein in vivo. We characterized cell membrane penetration ability of pIL-1αNLS or its tandem repeated form (2pIL-1αNLS) to enhance its intracellular delivery efficiency. 2pIL-1αNLS showed comparable protein delivery efficiency to TAT–CPP and it mediates endocytosis following heparan sulfate interaction. 2pIL-1αNLS conjugated enhanced green fluorescence protein was localized to the nucleus and the cytoplasm. Intra-peritoneal administration of 2pIL-1αNLS conjugated dTomato protein showed remarkable in vivo intracellular delivery efficiency in various tissues including spleen, liver, and intestine in mice. Moreover, cytotoxicity of 2pIL-1αNLS was not observed even at 100 μM. Our results demonstrate cell membrane-penetrating function of NLS in pIL-1α, which can be used as a safe therapeutic macromolecular delivery peptide. |
| Starting Page | 8117 |
| Ending Page | 8126 |
| Page Count | 10 |
| File Format | |
| ISSN | 03014851 |
| Journal | Molecular Biology Reports |
| Volume Number | 41 |
| Issue Number | 12 |
| e-ISSN | 15734978 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2014-09-10 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | IL-1α Cytokine Nuclear localization sequence Cell penetrating peptide Animal Biochemistry Animal Anatomy / Morphology / Histology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Medicine Molecular Biology |
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