{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:53:45Z","timestamp":1789883625257,"version":"4.0.1"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T00:00:00Z","timestamp":1518048000000},"content-version":"vor","delay-in-days":38,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["40102636"],"award-info":[{"award-number":["40102636"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>RNA\u2010binding protein dysregulation and altered expression of proteins involved in the autophagy\/proteasome pathway play a role in many neurodegenerative disease onset\/progression, including age\u2010related macular degeneration (AMD). HuR\/ELAVL1 is a master regulator of gene expression in human physiopathology. In ARPE\u201019 cells exposed to the proteasomal inhibitor MG132, HuR positively affects at posttranscriptional level p62 expression, a stress response gene involved in protein aggregate clearance with a role in AMD. Here, we studied the early effects of the proautophagy AICAR\u2009+\u2009MG132 cotreatment on the HuR\u2010p62 pathway. We treated ARPE\u201019 cells with Erk1\/2, AMPK, p38<jats:sup>MAPK<\/jats:sup>, PKC, and JNK kinase inhibitors in the presence of AICAR\u2009+\u2009MG132 and evaluated HuR localization\/phosphorylation and p62 expression. Two\u2010hour AICAR\u2009+\u2009MG132 induces both HuR cytoplasmic translocation and threonine phosphorylation via the Erk1\/2 pathway. In these conditions, p62 mRNA is loaded on polysomes and its translation in de novo protein is favored. Additionally, for the first time, we report that JNK can phosphorylate HuR, however, without modulating its localization. Our study supports HuR\u2019s role as an upstream regulator of p62 expression in ARPE\u201019 cells, helps to understand better the early events in response to a proautophagy stimulus, and suggests that modulation of the autophagy\u2010regulating kinases as potential therapeutic targets for AMD may be relevant.<\/jats:p>","DOI":"10.1155\/2018\/4956080","type":"journal-article","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T23:32:12Z","timestamp":1518132732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Autophagy Stimulus Promotes Early HuR Protein Activation and p62\/SQSTM1 Protein Synthesis in ARPE\u201019 Cells by Triggering Erk1\/2, p38<sup>MAPK<\/sup>, and JNK Kinase Pathways"],"prefix":"10.1155","volume":"2018","author":[{"given":"Nicoletta","family":"Marchesi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natthakan","family":"Thongon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Pascale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Provenzani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Koskela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveliina","family":"Korhonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8528-955X","authenticated-orcid":false,"given":"Adrian","family":"Smedowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Govoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8254-0200","authenticated-orcid":false,"given":"Anu","family":"Kauppinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaarniranta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5263-9306","authenticated-orcid":false,"given":"Marialaura","family":"Amadio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,8]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0810-7"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.02.050"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1355"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1394"},{"key":"e_1_2_7_5_2","first-page":"2154","article-title":"HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3\u2009\u2032 untranslated regions of cytokine and angiogenic factor mRNAs","volume":"61","author":"Nabors L. 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