Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7749
Authors: Gribko, Alena
Hahlbrock, Angelina
Strieth, Sebastian
Becker, Sven
Hagemann, Jan
Deichelbohrer, Max
Hildebrandt, Andreas
Habtemichael, Negusse
Wünsch, Désirée
Title: Disease-relevant signalling-pathways in head and neck cancer : Taspase1’s proteolytic activity fine-tunes TFIIA function
Online publication date: 14-Sep-2022
Year of first publication: 2017
Language: english
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: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
FB 08 Physik, Mathematik u. Informatik
Place: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-7749
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
Information on rights of use: https://creativecommons.org/licenses/by/4.0/
Journal: Scientific reports
7
Pages or article number: Art. 14937
Publisher: Macmillan Publishers Limited, part of Springer Nature
Publisher place: London
Issue date: 2017
ISSN: 2045-2322
Publisher URL: http://dx.doi.org/10.1038/s41598-017-14814-x
Publisher DOI: 10.1038/s41598-017-14814-x
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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