Universität zu Köln

Taute, Stefanie, Boehnke, Philipp, Sprissler, Jasmin, Buchholz, Stephanie, Hufbauer, Martin ORCID: 0000-0003-4106-0520, Akguel, Baki and Steger, Gertrud (2019). The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene. Cells, 8 (3). BASEL: MDPI. ISSN 2073-4409

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Abstract

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 beta HPV 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 beta HPVE6 proteins support proliferation of infected keratinocytes, thus creating an environment with increased risk of development of skin cancer particularly upon UV-induced DNA mutations.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Taute, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehnke, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Sprissler, Jasmin UNSPECIFIED UNSPECIFIED UNSPECIFIED Buchholz, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hufbauer, Martin UNSPECIFIED orcid.org/0000-0003-4106-0520 UNSPECIFIED Akguel, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED Steger, Gertrud UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-153768
DOI:	10.3390/cells8030244
Journal or Publication Title:	Cells
Volume:	8
Number:	3
Date:	2019
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SKIN TUMORIGENESIS; CELL-PROLIFERATION; RAS TRANSFORMATION; ESTROGEN-RECEPTOR; HPV 5; EXPRESSION; GROWTH; ACTIVATION; INHIBITION; P38-GAMMA Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15376