Universität zu Köln

Akguel, Baki, Kirschberg, Matthias ORCID: 0000-0002-3682-7371, Storey, Alan ORCID: 0000-0003-2001-9772 and Hufbauer, Martin ORCID: 0000-0003-4106-0520 (2019). Human papillomavirus type 8 oncoproteins E6 and E7 cooperate in downregulation of the cellular checkpoint kinase-1. Int. J. Cancer, 145 (3). S. 797 - 807. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

Human papillomavirus 8 (HPV8) is associated with the development of squamous cell carcinoma (SCC) of the skin. HPV-infected keratinocytes are able to override normal checkpoint control mechanisms and sustain cell cycle activity, allowing for synthesis of cellular proteins necessary for viral genome amplification. To study how HPV8 may disrupt cell cycle control, we analyzed the impact of HPV8 early gene expression on one of the key regulators of cell cycle and DNA damage response, checkpoint kinase-1 (CHK1). We found that expression of E1, E1E4, E2, E6 or E7 individually did not affect CHK1; however, keratinocytes expressing the complete early genome region (CER) of HPV8 showed a profound loss of CHK1 protein levels, that proved to be mediated by E6E7 co-expression. Neither CHK1 promoter regulation nor the ubiquitin-proteasome pathway are involved in HPV8-mediated CHK1 repression. However, CHK1 protein repression in organotypic skin cultures was paralleled by downregulation of the autophagy marker LC3B. Treatment of HPV8-CER expressing cells with the autophagy inhibitor Bafilomycin A1 rescued CHK1 expression and led to LC3B accumulation. Taken together, our data implicate that CHK1 autophagic degradation is enhanced by HPV8, which may contribute to the oncogenic potential of the virus.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Akguel, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirschberg, Matthias UNSPECIFIED orcid.org/0000-0002-3682-7371 UNSPECIFIED Storey, Alan UNSPECIFIED orcid.org/0000-0003-2001-9772 UNSPECIFIED Hufbauer, Martin UNSPECIFIED orcid.org/0000-0003-4106-0520 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-134387
DOI:	10.1002/ijc.32223
Journal or Publication Title:	Int. J. Cancer
Volume:	145
Number:	3
Page Range:	S. 797 - 807
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN CHK1; MALIGNANT-TRANSFORMATION; EARLY GENES; AUTOPHAGY; PROTEIN; REPLICATION; DEGRADATION; EXPRESSION; TARGETS; PHOSPHORYLATION Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13438