2026-06-14T04:01:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/106322025-06-13T10:32:32Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16977col_20.500.12105_19617
Repisalud
author
Gutiérrez-Salmerón, María
author
García-Martínez, José Manuel
author
Martínez-Useros, Javier
author
Fernández-Aceñero, María Jesús
author
Viollet, Benoit
author
Olivier, Severine
author
Chauhan, Jagat
author
Chocarro-Calvo, Ana
author
García-Jiménez, Custodia
author
De la Vieja, Antonio
author
Lucena, Silvia R.
author
Goding, Colin R.
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea
funder
European Molecular Biology Organization
funder
Comunidad de Madrid (España)
funder
Institut National de la Santé et de la Recherche Médicale (Francia)
funder
Agencia Estatal de Investigación (España)
2020-07-02T06:35:01Z
2020-07-02T06:35:01Z
2020-06
PLoS Biol. 2020 Jun 30;18(6):e3000732.
10.1371/journal.pbio.3000732
1545-7885
PLoS biology
32603375
http://hdl.handle.net/20.500.12105/10632
Coordination of gene expression with nutrient availability supports proliferation and homeostasis and is shaped by protein acetylation. Yet how physiological/pathological signals link acetylation to specific gene expression programs and whether such responses are cell-type-specific is unclear. AMP-activated protein kinase (AMPK) is a key energy sensor, activated by glucose limitation to resolve nutrient supply-demand imbalances, critical for diabetes and cancer. Unexpectedly, we show here that, in gastrointestinal cancer cells, glucose activates AMPK to selectively induce EP300, but not CREB-binding protein (CBP). Consequently, EP300 is redirected away from nuclear receptors that promote differentiation towards β-catenin, a driver of proliferation and colorectal tumorigenesis. Importantly, blocking glycogen synthesis permits reactive oxygen species (ROS) accumulation and AMPK activation in response to glucose in previously nonresponsive cells. Notably, glycogen content and activity of the ROS/AMPK/EP300/β-catenin axis are opposite in healthy versus tumor sections. Glycogen content reduction from healthy to tumor tissue may explain AMPK switching from tumor suppressor to activator during tumor evolution.
eng
Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer
research article
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https://repisalud.isciii.es/bitstreams/650ad8ab-43ff-42cd-9e7f-0900e6c012d5/download
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ParadoxicalActivationOfAMPK_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/1e11981a-ca6f-46f4-aea6-6a1083de7003/download
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text/plain
ParadoxicalActivationOfAMPK_2020.pdf.txt