Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy.

Authors:
Kevin Moreau
Kevin Moreau
Cambridge Institute for Medical Research
United Kingdom
Ghita Ghislat
Ghita Ghislat
Centro de Investigación Príncipe Felipe
Spain
Warren Hochfeld
Warren Hochfeld
Cambridge Institute for Medical Research
Maurizio Renna
Maurizio Renna
Cambridge Institute for Medical Research
United Kingdom
Eszter Zavodszky
Eszter Zavodszky
Addenbrooke's Hospital
United Kingdom
Gautam Runwal
Gautam Runwal
Cambridge Institute for Medical Research
Claudia Puri
Claudia Puri
Cambridge Institute for Medical Research
United Kingdom
Shirley Lee
Shirley Lee
University of Toronto
Canada

Nat Commun 2015 Aug 20;6:8045. Epub 2015 Aug 20.

Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, UK.

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.

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http://dx.doi.org/10.1038/ncomms9045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560779PMC
August 2015
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