The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene
Human papillomaviruses (HPV) replicate their DNA in the suprabasal layer of the infected mucosa or skin. In order to create a suitable environment for vegetative viral DNA replication HPV delay differentiation and sustain keratinocyte proliferation that can lead to hyperplasia. The mechanism underly...
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MDPI AG
2019-03-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/8/3/244 |
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| author | Stefanie Taute Philipp Böhnke Jasmin Sprissler Stephanie Buchholz Martin Hufbauer Baki Akgül Gertrud Steger |
| author_facet | Stefanie Taute Philipp Böhnke Jasmin Sprissler Stephanie Buchholz Martin Hufbauer Baki Akgül Gertrud Steger |
| author_sort | Stefanie Taute |
| collection | DOAJ |
| description | Human papillomaviruses (HPV) replicate their DNA in the suprabasal layer of the infected mucosa or skin. In order to create a suitable environment for vegetative viral DNA replication HPV delay differentiation and sustain keratinocyte proliferation that can lead to hyperplasia. The mechanism underlying cell growth stimulation is not well characterized. Here, we show that the E6 oncoprotein of the βHPV type 8 (HPV8), which infects the cutaneous skin and is associated with skin cancer in Epidermodysplasia verruciformis patients and immunosuppressed organ transplant recipients, binds to the protein tyrosine phosphatase H1 (PTPH1), which resulted in increased protein expression and phosphatase activity of PTPH1. Suppression of PTPH1 in immortalized keratinocytes reduced cell proliferation as well as the level of epidermal growth factor receptor (EGFR). Furthermore, we report that HPV8E6 expressing keratinocytes have increased level of active, GTP-bound Ras. This effect was independent of PTPH1. Therefore, HPV8E6-mediated targeting of PTPH1 might result in higher level of EGFR and enhanced keratinocyte proliferation. The HPV8E6-mediated stimulation of Ras may be an additional step to induce cell growth. Our results provide novel insights into the mechanism how βHPVE6 proteins support proliferation of infected keratinocytes, thus creating an environment with increased risk of development of skin cancer particularly upon UV-induced DNA mutations. |
| first_indexed | 2024-03-12T07:33:07Z |
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| language | English |
| last_indexed | 2024-03-12T07:33:07Z |
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| spelling | doaj.art-591518edcdb747a6b66728e836d85c3f2023-09-02T21:36:30ZengMDPI AGCells2073-44092019-03-018324410.3390/cells8030244cells8030244The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 OncogeneStefanie Taute0Philipp Böhnke1Jasmin Sprissler2Stephanie Buchholz3Martin Hufbauer4Baki Akgül5Gertrud Steger6Institute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, GermanyInstitute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, GermanyInstitute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, GermanyInstitute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, GermanyInstitute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, GermanyInstitute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, GermanyInstitute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, GermanyHuman papillomaviruses (HPV) replicate their DNA in the suprabasal layer of the infected mucosa or skin. In order to create a suitable environment for vegetative viral DNA replication HPV delay differentiation and sustain keratinocyte proliferation that can lead to hyperplasia. The mechanism underlying cell growth stimulation is not well characterized. Here, we show that the E6 oncoprotein of the βHPV type 8 (HPV8), which infects the cutaneous skin and is associated with skin cancer in Epidermodysplasia verruciformis patients and immunosuppressed organ transplant recipients, binds to the protein tyrosine phosphatase H1 (PTPH1), which resulted in increased protein expression and phosphatase activity of PTPH1. Suppression of PTPH1 in immortalized keratinocytes reduced cell proliferation as well as the level of epidermal growth factor receptor (EGFR). Furthermore, we report that HPV8E6 expressing keratinocytes have increased level of active, GTP-bound Ras. This effect was independent of PTPH1. Therefore, HPV8E6-mediated targeting of PTPH1 might result in higher level of EGFR and enhanced keratinocyte proliferation. The HPV8E6-mediated stimulation of Ras may be an additional step to induce cell growth. Our results provide novel insights into the mechanism how βHPVE6 proteins support proliferation of infected keratinocytes, thus creating an environment with increased risk of development of skin cancer particularly upon UV-induced DNA mutations.http://www.mdpi.com/2073-4409/8/3/244Human papillomaviruses (HPV)HPV8E6 oncoproteinprotein tyrosine phosphatase H1 (PTPH1)EGFRactive Raskeratinocyte proliferation |
| spellingShingle | Stefanie Taute Philipp Böhnke Jasmin Sprissler Stephanie Buchholz Martin Hufbauer Baki Akgül Gertrud Steger The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene Cells Human papillomaviruses (HPV) HPV8 E6 oncoprotein protein tyrosine phosphatase H1 (PTPH1) EGFR active Ras keratinocyte proliferation |
| title | The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene |
| title_full | The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene |
| title_fullStr | The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene |
| title_full_unstemmed | The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene |
| title_short | The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene |
| title_sort | protein tyrosine phosphatase h1 ptph1 supports proliferation of keratinocytes and is a target of the human papillomavirus type 8 e6 oncogene |
| topic | Human papillomaviruses (HPV) HPV8 E6 oncoprotein protein tyrosine phosphatase H1 (PTPH1) EGFR active Ras keratinocyte proliferation |
| url | http://www.mdpi.com/2073-4409/8/3/244 |
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