Gutenberg Open Science: Disease-relevant signalling-pathways in head and neck cancer : Taspase1’s proteolytic activity fine-tunes TFIIA function

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7749

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DC Field	Value	Language
dc.contributor.author	Gribko, Alena	-
dc.contributor.author	Hahlbrock, Angelina	-
dc.contributor.author	Strieth, Sebastian	-
dc.contributor.author	Becker, Sven	-
dc.contributor.author	Hagemann, Jan	-
dc.contributor.author	Deichelbohrer, Max	-
dc.contributor.author	Hildebrandt, Andreas	-
dc.contributor.author	Habtemichael, Negusse	-
dc.contributor.author	Wünsch, Désirée	-
dc.date.accessioned	2022-09-14T07:56:39Z	-
dc.date.available	2022-09-14T07:56:39Z	-
dc.date.issued	2017
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7764	-
dc.description.abstract	Head and neck cancer (HNC) is the seventh most common malignancy in the world and its prevailing form, the head and neck squamous cell carcinoma (HNSCC), is characterized as aggressive and invasive cancer type. The transcription factor II A (TFIIA), initially described as general regulator of RNA polymerase II-dependent transcription, is part of complex transcriptional networks also controlling mammalian head morphogenesis. Posttranslational cleavage of the TFIIA precursor by the oncologically relevant protease Taspase1 is crucial in this process. In contrast, the relevance of Taspase1-mediated TFIIA cleavage during oncogenesis of HNSCC is not characterized yet. Here, we performed genome-wide expression profiling of HNSCC which revealed significant downregulation of the TFIIA downstream target CDKN2A. To identify potential regulatory mechanisms of TFIIA on cellular level, we characterized nuclear-cytoplasmic transport and Taspase1-mediated cleavage of TFIIA variants. Unexpectedly, we identified an evolutionary conserved nuclear export signal (NES) counteracting nuclear localization and thus, transcriptional activity of TFIIA. Notably, proteolytic processing of TFIIA by Taspase1 was found to mask the NES, thereby promoting nuclear localization and transcriptional activation of TFIIA target genes, such as CDKN2A. Collectively, we here describe a hitherto unknown mechanism how cellular localization and Taspase1 cleavage fine-tunes transcriptional activity of TFIIA in HNSCC.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Disease-relevant signalling-pathways in head and neck cancer : Taspase1’s proteolytic activity fine-tunes TFIIA function	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7749	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.department	FB 08 Physik, Mathematik u. Informatik	de
jgu.organisation.number	2700	-
jgu.organisation.number	7940	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Scientific reports	de
jgu.journal.volume	7	de
jgu.pages.alternative	Art. 14937	de
jgu.publisher.year	2017	-
jgu.publisher.name	Macmillan Publishers Limited, part of Springer Nature	de
jgu.publisher.place	London	de
jgu.publisher.uri	http://dx.doi.org/10.1038/s41598-017-14814-x	de
jgu.publisher.issn	2045-2322	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
opus.date.modified	2018-04-04T08:57:55Z
opus.subject.dfgcode	00-000
opus.organisation.string	FB 04: Medizin: Hals-, Nasen- und Ohren-Klinik und Poliklinik	de_DE
opus.organisation.string	FB 08: Physik, Mathematik und Informatik: Institut für Informatik	de_DE
opus.identifier.opusid	58011
opus.institute.number	0447
opus.institute.number	0805
opus.metadataonly	false
opus.type.contenttype	Keine	de_DE
opus.type.contenttype	None	en_EN
opus.affiliated	Strieth, Sebastian
opus.affiliated	Becker, Sven
opus.affiliated	Hildebrandt, Andreas
opus.affiliated	Wünsch, Désirée
jgu.publisher.doi	10.1038/s41598-017-14814-x	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

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