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) |
Files in This Item:
File | Description | Size | Format | ||
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diseaserelevant_signallingpat-20220913191301676.pdf | 4.15 MB | Adobe PDF | View/Open |