Functional Study of the Retrotransposon-Derived Human PEG10 Protease
Paternally expressed gene 10 (PEG10) is a human retrotransposon-derived imprinted gene. The mRNA of <i>PEG10</i> encodes two protein isoforms: the Gag-like protein (RF1<sub>PEG10</sub>) is coded by reading frame 1, while the Gag-Pol-like polyprotein (RF1/RF2<sub>PEG10&l...
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MDPI AG
2020-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2424 |
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| author | Mária Golda János András Mótyán Mohamed Mahdi József Tőzsér |
| author_facet | Mária Golda János András Mótyán Mohamed Mahdi József Tőzsér |
| author_sort | Mária Golda |
| collection | DOAJ |
| description | Paternally expressed gene 10 (PEG10) is a human retrotransposon-derived imprinted gene. The mRNA of <i>PEG10</i> encodes two protein isoforms: the Gag-like protein (RF1<sub>PEG10</sub>) is coded by reading frame 1, while the Gag-Pol-like polyprotein (RF1/RF2<sub>PEG10</sub>) is coded by reading frames 1 and 2. The proteins are translated by a typical retroviral frameshift mechanism. The protease (PR) domain of RF2<sub>PEG10</sub> contains an -Asp-Ser-Gly- sequence, which corresponds to the consensus -Asp-Ser/Thr-Gly- active-site motif of retroviral aspartic proteases. The function of the aspartic protease domain of RF2<sub>PEG10</sub> remains unclear. To elucidate the function of PEG10 protease (PR<sub>PEG10</sub>), we designed a frameshift mutant (<sub>fs</sub>RF1/RF2<sub>PEG10</sub>) for comparison with the RF1/RF2<sub>PEG10</sub> form. To study the effects of PR<sub>PEG10 </sub>on cellular proliferation and viability, mammalian HEK293T and HaCaT cells were transfected with plasmids coding for either RF1/RF2<sub>PEG10</sub>, the frameshift mutant (<sub>fs</sub>RF1/RF2<sub>PEG10</sub>), or a PR active-site (D370A) mutant <sub>fs</sub>RF1/RF2<sub>PEG10</sub>. Our results indicate that <sub>fs</sub>RF1/RF2<sub>PEG10 </sub>overexpression results in increased cellular proliferation. Remarkably, transfection with <sub>fs</sub>RF1/RF2<sub>PEG10</sub> had a detrimental effect on cell viability. We hypothesize that PR<sub>PEG10</sub> plays an important role in the function of this retroviral remnant, mediating the proliferation of cells and possibly implicating it in the inhibition of apoptosis. |
| first_indexed | 2024-03-10T20:47:21Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:47:21Z |
| publishDate | 2020-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ead1e5c7b66846fabb2b46c4efdd153d2023-11-19T20:17:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-03-01217242410.3390/ijms21072424Functional Study of the Retrotransposon-Derived Human PEG10 ProteaseMária Golda0János András Mótyán1Mohamed Mahdi2József Tőzsér3Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryPaternally expressed gene 10 (PEG10) is a human retrotransposon-derived imprinted gene. The mRNA of <i>PEG10</i> encodes two protein isoforms: the Gag-like protein (RF1<sub>PEG10</sub>) is coded by reading frame 1, while the Gag-Pol-like polyprotein (RF1/RF2<sub>PEG10</sub>) is coded by reading frames 1 and 2. The proteins are translated by a typical retroviral frameshift mechanism. The protease (PR) domain of RF2<sub>PEG10</sub> contains an -Asp-Ser-Gly- sequence, which corresponds to the consensus -Asp-Ser/Thr-Gly- active-site motif of retroviral aspartic proteases. The function of the aspartic protease domain of RF2<sub>PEG10</sub> remains unclear. To elucidate the function of PEG10 protease (PR<sub>PEG10</sub>), we designed a frameshift mutant (<sub>fs</sub>RF1/RF2<sub>PEG10</sub>) for comparison with the RF1/RF2<sub>PEG10</sub> form. To study the effects of PR<sub>PEG10 </sub>on cellular proliferation and viability, mammalian HEK293T and HaCaT cells were transfected with plasmids coding for either RF1/RF2<sub>PEG10</sub>, the frameshift mutant (<sub>fs</sub>RF1/RF2<sub>PEG10</sub>), or a PR active-site (D370A) mutant <sub>fs</sub>RF1/RF2<sub>PEG10</sub>. Our results indicate that <sub>fs</sub>RF1/RF2<sub>PEG10 </sub>overexpression results in increased cellular proliferation. Remarkably, transfection with <sub>fs</sub>RF1/RF2<sub>PEG10</sub> had a detrimental effect on cell viability. We hypothesize that PR<sub>PEG10</sub> plays an important role in the function of this retroviral remnant, mediating the proliferation of cells and possibly implicating it in the inhibition of apoptosis.https://www.mdpi.com/1422-0067/21/7/2424PEG10paternally expressed gene 10cell viabilitycell proliferationcis protease activityubiquitination |
| spellingShingle | Mária Golda János András Mótyán Mohamed Mahdi József Tőzsér Functional Study of the Retrotransposon-Derived Human PEG10 Protease International Journal of Molecular Sciences PEG10 paternally expressed gene 10 cell viability cell proliferation cis protease activity ubiquitination |
| title | Functional Study of the Retrotransposon-Derived Human PEG10 Protease |
| title_full | Functional Study of the Retrotransposon-Derived Human PEG10 Protease |
| title_fullStr | Functional Study of the Retrotransposon-Derived Human PEG10 Protease |
| title_full_unstemmed | Functional Study of the Retrotransposon-Derived Human PEG10 Protease |
| title_short | Functional Study of the Retrotransposon-Derived Human PEG10 Protease |
| title_sort | functional study of the retrotransposon derived human peg10 protease |
| topic | PEG10 paternally expressed gene 10 cell viability cell proliferation cis protease activity ubiquitination |
| url | https://www.mdpi.com/1422-0067/21/7/2424 |
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