Autoren:	Gribko, Alena Hahlbrock, Angelina Strieth, Sebastian Becker, Sven Hagemann, Jan Deichelbohrer, Max Hildebrandt, Andreas Habtemichael, Negusse Wünsch, Désirée
Titel:	Disease-relevant signalling-pathways in head and neck cancer : Taspase1’s proteolytic activity fine-tunes TFIIA function
Online-Publikationsdatum:	14-Sep-2022
Erscheinungsdatum:	2017
Sprache des Dokuments:	Englisch
Zusammenfassung/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.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin FB 08 Physik, Mathematik u. Informatik
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7749
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Scientific reports 7
Seitenzahl oder Artikelnummer:	Art. 14937
Verlag:	Macmillan Publishers Limited, part of Springer Nature
Verlagsort:	London
Erscheinungsdatum:	2017
ISSN:	2045-2322
URL der Originalveröffentlichung:	http://dx.doi.org/10.1038/s41598-017-14814-x
DOI der Originalveröffentlichung:	10.1038/s41598-017-14814-x
Enthalten in den Sammlungen:	DFG-OA-Publizieren (2012 - 2017)