Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of proteotoxic and oxidative stress
The polyubiquitin gene ubiquitin C (UBC) is considered a stress protective gene and is upregulated under various stressful conditions, which is probably a consequence of an increased demand for ubiquitin in order to remove toxic misfolded proteins. We previously identified heat shock elements (HSEs)...
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| Format: | Article |
| Language: | English |
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Wiley
2018-09-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12484 |
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| author | Marzia Bianchi Rita Crinelli Vanessa Arbore Mauro Magnani |
| author_facet | Marzia Bianchi Rita Crinelli Vanessa Arbore Mauro Magnani |
| author_sort | Marzia Bianchi |
| collection | DOAJ |
| description | The polyubiquitin gene ubiquitin C (UBC) is considered a stress protective gene and is upregulated under various stressful conditions, which is probably a consequence of an increased demand for ubiquitin in order to remove toxic misfolded proteins. We previously identified heat shock elements (HSEs) within the UBC promoter, which are responsible for heat shock factor (HSF)1‐driven induction of the UBC gene and are activated by proteotoxic stress. Here, we determined the molecular players driving the UBC gene transcriptional response to arsenite treatment, mainly addressing the role of the nuclear factor‐erythroid 2‐related factor 2 (Nrf2)‐mediated antioxidant pathway. Exposure of HeLa cells to arsenite caused a time‐dependent increase of UBC mRNA, while cell viability and proteasome activity were not affected. Nuclear accumulation of HSF1 and Nrf2 transcription factors was detected upon both arsenite and MG132 treatment, while HSF2 nuclear levels increased in MG132‐treated cells. Notably, siRNA‐mediated knockdown of Nrf2 did not reduce UBC transcription under either basal or stressful conditions, but significantly impaired the constitutive and inducible expression of well‐known antioxidant response element‐dependent genes. A chromatin immunoprecipitation assay consistently failed to detect Nrf2 binding to the UBC promoter sequence. By contrast, depletion of HSF1, but not HSF2, significantly compromised stress‐induced UBC expression. Critically, HSF1‐mediated UBC trans‐activation upon arsenite exposure relies on transcription factor binding to previously mapped distal HSEs, as demonstrated to occur under proteasome inhibition. These data highlight HSF1 as the pivotal transcription factor that translates different stress signals into UBC gene transcriptional induction. |
| first_indexed | 2024-04-10T00:37:52Z |
| format | Article |
| id | doaj.art-cfeae6dd2d354db09f532e16ca8c8a61 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-10T00:37:52Z |
| publishDate | 2018-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-cfeae6dd2d354db09f532e16ca8c8a612023-03-14T13:05:47ZengWileyFEBS Open Bio2211-54632018-09-01891471148510.1002/2211-5463.12484Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of proteotoxic and oxidative stressMarzia Bianchi0Rita Crinelli1Vanessa Arbore2Mauro Magnani3Department of Biomolecular Sciences, Biochemistry and Molecular Biology Section University of Urbino ‘Carlo Bo’ ItalyDepartment of Biomolecular Sciences, Biochemistry and Molecular Biology Section University of Urbino ‘Carlo Bo’ ItalyDepartment of Biomolecular Sciences, Biochemistry and Molecular Biology Section University of Urbino ‘Carlo Bo’ ItalyDepartment of Biomolecular Sciences, Biochemistry and Molecular Biology Section University of Urbino ‘Carlo Bo’ ItalyThe polyubiquitin gene ubiquitin C (UBC) is considered a stress protective gene and is upregulated under various stressful conditions, which is probably a consequence of an increased demand for ubiquitin in order to remove toxic misfolded proteins. We previously identified heat shock elements (HSEs) within the UBC promoter, which are responsible for heat shock factor (HSF)1‐driven induction of the UBC gene and are activated by proteotoxic stress. Here, we determined the molecular players driving the UBC gene transcriptional response to arsenite treatment, mainly addressing the role of the nuclear factor‐erythroid 2‐related factor 2 (Nrf2)‐mediated antioxidant pathway. Exposure of HeLa cells to arsenite caused a time‐dependent increase of UBC mRNA, while cell viability and proteasome activity were not affected. Nuclear accumulation of HSF1 and Nrf2 transcription factors was detected upon both arsenite and MG132 treatment, while HSF2 nuclear levels increased in MG132‐treated cells. Notably, siRNA‐mediated knockdown of Nrf2 did not reduce UBC transcription under either basal or stressful conditions, but significantly impaired the constitutive and inducible expression of well‐known antioxidant response element‐dependent genes. A chromatin immunoprecipitation assay consistently failed to detect Nrf2 binding to the UBC promoter sequence. By contrast, depletion of HSF1, but not HSF2, significantly compromised stress‐induced UBC expression. Critically, HSF1‐mediated UBC trans‐activation upon arsenite exposure relies on transcription factor binding to previously mapped distal HSEs, as demonstrated to occur under proteasome inhibition. These data highlight HSF1 as the pivotal transcription factor that translates different stress signals into UBC gene transcriptional induction.https://doi.org/10.1002/2211-5463.12484HSF1Nrf2proteostasisstress responseUBC geneubiquitin upregulation |
| spellingShingle | Marzia Bianchi Rita Crinelli Vanessa Arbore Mauro Magnani Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of proteotoxic and oxidative stress FEBS Open Bio HSF1 Nrf2 proteostasis stress response UBC gene ubiquitin upregulation |
| title | Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of proteotoxic and oxidative stress |
| title_full | Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of proteotoxic and oxidative stress |
| title_fullStr | Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of proteotoxic and oxidative stress |
| title_full_unstemmed | Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of proteotoxic and oxidative stress |
| title_short | Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of proteotoxic and oxidative stress |
| title_sort | induction of ubiquitin c ubc gene transcription is mediated by hsf1 role of proteotoxic and oxidative stress |
| topic | HSF1 Nrf2 proteostasis stress response UBC gene ubiquitin upregulation |
| url | https://doi.org/10.1002/2211-5463.12484 |
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