Loss of p19Arf promotes fibroblast survival during leucine deprivation
Fibroblasts are quiescent and tumor suppressive in nature but become activated in wound healing and cancer. The response of fibroblasts to cellular stress has not been extensively investigated, however the p53 tumor suppressor has been shown to be activated in fibroblasts during nutrient deprivation...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2022-02-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/11/2/bio058728 |
| _version_ | 1831766634290741248 |
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| author | Kerry C. Roby Allyson Lieberman Bang-Jin Kim Nicole Zaragoza Rodríguez Jessica M. Posimo Tiffany Tsang Ioannis I. Verginadis Ellen Puré Donita C. Brady Constantinos Koumenis Sandra Ryeom |
| author_facet | Kerry C. Roby Allyson Lieberman Bang-Jin Kim Nicole Zaragoza Rodríguez Jessica M. Posimo Tiffany Tsang Ioannis I. Verginadis Ellen Puré Donita C. Brady Constantinos Koumenis Sandra Ryeom |
| author_sort | Kerry C. Roby |
| collection | DOAJ |
| description | Fibroblasts are quiescent and tumor suppressive in nature but become activated in wound healing and cancer. The response of fibroblasts to cellular stress has not been extensively investigated, however the p53 tumor suppressor has been shown to be activated in fibroblasts during nutrient deprivation. Since the p19 Alternative reading frame (p19Arf) tumor suppressor is a key regulator of p53 activation during oncogenic stress, we investigated the role of p19Arf in fibroblasts during nutrient deprivation. Here, we show that prolonged leucine deprivation results in increased expression and nuclear localization of p19Arf, triggering apoptosis in primary murine adult lung fibroblasts (ALFs). In contrast, the absence of p19Arf during long-term leucine deprivation resulted in increased ALF proliferation, migration and survival through upregulation of the Integrated Stress Response pathway and increased autophagic flux. Our data implicates a new role for p19Arf in response to nutrient deprivation. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-12-22T06:26:20Z |
| format | Article |
| id | doaj.art-2d75c0195d6f44f185ece86f67e5048f |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-22T06:26:20Z |
| publishDate | 2022-02-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-2d75c0195d6f44f185ece86f67e5048f2022-12-21T18:35:50ZengThe Company of BiologistsBiology Open2046-63902022-02-0111210.1242/bio.058728058728Loss of p19Arf promotes fibroblast survival during leucine deprivationKerry C. Roby0Allyson Lieberman1Bang-Jin Kim2Nicole Zaragoza Rodríguez3Jessica M. Posimo4Tiffany Tsang5Ioannis I. Verginadis6Ellen Puré7Donita C. Brady8Constantinos Koumenis9Sandra Ryeom10 Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Fibroblasts are quiescent and tumor suppressive in nature but become activated in wound healing and cancer. The response of fibroblasts to cellular stress has not been extensively investigated, however the p53 tumor suppressor has been shown to be activated in fibroblasts during nutrient deprivation. Since the p19 Alternative reading frame (p19Arf) tumor suppressor is a key regulator of p53 activation during oncogenic stress, we investigated the role of p19Arf in fibroblasts during nutrient deprivation. Here, we show that prolonged leucine deprivation results in increased expression and nuclear localization of p19Arf, triggering apoptosis in primary murine adult lung fibroblasts (ALFs). In contrast, the absence of p19Arf during long-term leucine deprivation resulted in increased ALF proliferation, migration and survival through upregulation of the Integrated Stress Response pathway and increased autophagic flux. Our data implicates a new role for p19Arf in response to nutrient deprivation. This article has an associated First Person interview with the first author of the paper.http://bio.biologists.org/content/11/2/bio058728p19arffibroblastleucine deprivationintegrated stress responseautophagy |
| spellingShingle | Kerry C. Roby Allyson Lieberman Bang-Jin Kim Nicole Zaragoza Rodríguez Jessica M. Posimo Tiffany Tsang Ioannis I. Verginadis Ellen Puré Donita C. Brady Constantinos Koumenis Sandra Ryeom Loss of p19Arf promotes fibroblast survival during leucine deprivation Biology Open p19arf fibroblast leucine deprivation integrated stress response autophagy |
| title | Loss of p19Arf promotes fibroblast survival during leucine deprivation |
| title_full | Loss of p19Arf promotes fibroblast survival during leucine deprivation |
| title_fullStr | Loss of p19Arf promotes fibroblast survival during leucine deprivation |
| title_full_unstemmed | Loss of p19Arf promotes fibroblast survival during leucine deprivation |
| title_short | Loss of p19Arf promotes fibroblast survival during leucine deprivation |
| title_sort | loss of p19arf promotes fibroblast survival during leucine deprivation |
| topic | p19arf fibroblast leucine deprivation integrated stress response autophagy |
| url | http://bio.biologists.org/content/11/2/bio058728 |
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