Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy
Autophagy is an important degradation pathway, which is induced after starvation, where it buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. While the classical pathway mediating this response is via mTOR inhibition, there are likely to be additional pathways t...
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Nature Pub. Group
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560779/ |
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pubmed-45607792015-09-14 Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy Moreau, Kevin Ghislat, Ghita Hochfeld, Warren Renna, Maurizio Zavodszky, Eszter Runwal, Gautam Puri, Claudia Lee, Shirley Siddiqi, Farah Menzies, Fiona M. Ravikumar, Brinda Rubinsztein, David C. Article Autophagy is an important degradation pathway, which is induced after starvation, where it buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. While the classical pathway mediating this response is via mTOR inhibition, there are likely to be additional pathways that support the process. Here, we identify Annexin A2 as an autophagy modulator that regulates autophagosome formation by enabling appropriate ATG9A trafficking from endosomes to autophagosomes via actin. This process is dependent on the Annexin A2 effectors ARP2 and Spire1. Annexin A2 expression increases after starvation in cells in an mTOR-independent fashion. This is mediated via Jun N-terminal kinase activation of c-Jun, which, in turn, enhances the trans-activation of the Annexin A2 promoter. Annexin A2 knockdown abrogates starvation-induced autophagy, while its overexpression induces autophagy. Hence, c-Jun-mediated transcriptional responses support starvation-induced autophagy by regulating Annexin A2 expression levels. Nature Pub. Group 2015-08-20 /pmc/articles/PMC4560779/ /pubmed/26289944 http://dx.doi.org/10.1038/ncomms9045 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Moreau, Kevin Ghislat, Ghita Hochfeld, Warren Renna, Maurizio Zavodszky, Eszter Runwal, Gautam Puri, Claudia Lee, Shirley Siddiqi, Farah Menzies, Fiona M. Ravikumar, Brinda Rubinsztein, David C. |
| spellingShingle |
Moreau, Kevin Ghislat, Ghita Hochfeld, Warren Renna, Maurizio Zavodszky, Eszter Runwal, Gautam Puri, Claudia Lee, Shirley Siddiqi, Farah Menzies, Fiona M. Ravikumar, Brinda Rubinsztein, David C. Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy |
| author_facet |
Moreau, Kevin Ghislat, Ghita Hochfeld, Warren Renna, Maurizio Zavodszky, Eszter Runwal, Gautam Puri, Claudia Lee, Shirley Siddiqi, Farah Menzies, Fiona M. Ravikumar, Brinda Rubinsztein, David C. |
| author_sort |
Moreau, Kevin |
| title |
Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy |
| title_short |
Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy |
| title_full |
Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy |
| title_fullStr |
Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy |
| title_full_unstemmed |
Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy |
| title_sort |
transcriptional regulation of annexin a2 promotes starvation-induced autophagy |
| description |
Autophagy is an important degradation pathway, which is induced after starvation, where it buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. While the classical pathway mediating this response is via mTOR inhibition, there are likely to be additional pathways that support the process. Here, we identify Annexin A2 as an autophagy modulator that regulates autophagosome formation by enabling appropriate ATG9A trafficking from endosomes to autophagosomes via actin. This process is dependent on the Annexin A2 effectors ARP2 and Spire1. Annexin A2 expression increases after starvation in cells in an mTOR-independent fashion. This is mediated via Jun N-terminal kinase activation of c-Jun, which, in turn, enhances the trans-activation of the Annexin A2 promoter. Annexin A2 knockdown abrogates starvation-induced autophagy, while its overexpression induces autophagy. Hence, c-Jun-mediated transcriptional responses support starvation-induced autophagy by regulating Annexin A2 expression levels. |
| publisher |
Nature Pub. Group |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560779/ |
| _version_ |
1613473031467827200 |