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Nucleolar AATF regulates c-Jun–mediated apoptosis
The AP-1 transcription factor c-Jun has been shown to be essential for stress-induced apoptosis in several models. However, the molecular mechanisms underlying the proapoptotic activity of c-Jun are poorly understood. We identify the apoptosis-antagonizing transcription factor (AATF) as a novel nucl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484108/ https://www.ncbi.nlm.nih.gov/pubmed/22933572 http://dx.doi.org/10.1091/mbc.E12-05-0419 |
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author | Ferraris, Saima E. Isoniemi, Kimmo Torvaldson, Elin Anckar, Julius Westermarck, Jukka Eriksson, John E. |
author_facet | Ferraris, Saima E. Isoniemi, Kimmo Torvaldson, Elin Anckar, Julius Westermarck, Jukka Eriksson, John E. |
author_sort | Ferraris, Saima E. |
collection | PubMed |
description | The AP-1 transcription factor c-Jun has been shown to be essential for stress-induced apoptosis in several models. However, the molecular mechanisms underlying the proapoptotic activity of c-Jun are poorly understood. We identify the apoptosis-antagonizing transcription factor (AATF) as a novel nucleolar stress sensor, which is required as a cofactor for c-Jun–mediated apoptosis. Overexpression or down-regulation of AATF expression levels led to a respective increase or decrease in the amount of activated and phosphorylated c-Jun with a proportional alteration in the induction levels of the proapoptotic c-Jun target genes FasL and TNF-α. Accordingly, AATF promoted commitment of ultraviolet (UV)-irradiated cells to c-Jun-dependent apoptosis. Whereas AATF overexpression potentiated UV-induced apoptosis in wild-type cells, c-Jun–deficient mouse embryonic fibroblasts were resistant to AATF-mediated apoptosis induction. Furthermore, AATF mutants defective in c-Jun binding were also defective in inducing AP-1 activity and c-Jun–mediated apoptosis. UV irradiation induced a translocation of AATF from the nucleolus to the nucleus, thereby enabling its physical association to c-Jun. Analysis of AATF deletion mutants revealed that the AATF domains required for compartmentalization, c-Jun binding, and enhancement of c-Jun transcriptional activity were all also required to induce c-Jun–dependent apoptosis. These results identify AATF as a nucleolar-confined c-Jun cofactor whose expression levels and spatial distribution determine the stress-induced activity of c-Jun and the levels of c-Jun–mediated apoptosis. |
format | Online Article Text |
id | pubmed-3484108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34841082013-01-16 Nucleolar AATF regulates c-Jun–mediated apoptosis Ferraris, Saima E. Isoniemi, Kimmo Torvaldson, Elin Anckar, Julius Westermarck, Jukka Eriksson, John E. Mol Biol Cell Articles The AP-1 transcription factor c-Jun has been shown to be essential for stress-induced apoptosis in several models. However, the molecular mechanisms underlying the proapoptotic activity of c-Jun are poorly understood. We identify the apoptosis-antagonizing transcription factor (AATF) as a novel nucleolar stress sensor, which is required as a cofactor for c-Jun–mediated apoptosis. Overexpression or down-regulation of AATF expression levels led to a respective increase or decrease in the amount of activated and phosphorylated c-Jun with a proportional alteration in the induction levels of the proapoptotic c-Jun target genes FasL and TNF-α. Accordingly, AATF promoted commitment of ultraviolet (UV)-irradiated cells to c-Jun-dependent apoptosis. Whereas AATF overexpression potentiated UV-induced apoptosis in wild-type cells, c-Jun–deficient mouse embryonic fibroblasts were resistant to AATF-mediated apoptosis induction. Furthermore, AATF mutants defective in c-Jun binding were also defective in inducing AP-1 activity and c-Jun–mediated apoptosis. UV irradiation induced a translocation of AATF from the nucleolus to the nucleus, thereby enabling its physical association to c-Jun. Analysis of AATF deletion mutants revealed that the AATF domains required for compartmentalization, c-Jun binding, and enhancement of c-Jun transcriptional activity were all also required to induce c-Jun–dependent apoptosis. These results identify AATF as a nucleolar-confined c-Jun cofactor whose expression levels and spatial distribution determine the stress-induced activity of c-Jun and the levels of c-Jun–mediated apoptosis. The American Society for Cell Biology 2012-11-01 /pmc/articles/PMC3484108/ /pubmed/22933572 http://dx.doi.org/10.1091/mbc.E12-05-0419 Text en © 2012 Ferraris et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Ferraris, Saima E. Isoniemi, Kimmo Torvaldson, Elin Anckar, Julius Westermarck, Jukka Eriksson, John E. Nucleolar AATF regulates c-Jun–mediated apoptosis |
title | Nucleolar AATF regulates c-Jun–mediated apoptosis |
title_full | Nucleolar AATF regulates c-Jun–mediated apoptosis |
title_fullStr | Nucleolar AATF regulates c-Jun–mediated apoptosis |
title_full_unstemmed | Nucleolar AATF regulates c-Jun–mediated apoptosis |
title_short | Nucleolar AATF regulates c-Jun–mediated apoptosis |
title_sort | nucleolar aatf regulates c-jun–mediated apoptosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484108/ https://www.ncbi.nlm.nih.gov/pubmed/22933572 http://dx.doi.org/10.1091/mbc.E12-05-0419 |
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