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- Publisher Website: 10.1016/j.molcel.2020.12.008
- Scopus: eid_2-s2.0-85099693218
- PMID: 33400924
- WOS: WOS:000632641500007
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Article: Negative regulation of AMPK signaling by high glucose via E3 ubiquitin ligase MG53
Title | Negative regulation of AMPK signaling by high glucose via E3 ubiquitin ligase MG53 |
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Authors | |
Issue Date | 2021 |
Publisher | Cell Press. The Journal's web site is located at http://www.elsevier.com/locate/molcel |
Citation | Molecular Cell, 2021, v. 81 n. 3, p. 629-637.e5 How to Cite? |
Abstract | As a master regulator of metabolism, AMP-activated protein kinase (AMPK) is activated upon energy and glucose shortage but suppressed upon overnutrition. Exaggerated negative regulation of AMPK signaling by nutrient overload plays a crucial role in metabolic diseases. However, the mechanism underlying the negative regulation is poorly understood. Here, we demonstrate that high glucose represses AMPK signaling via MG53 (also called TRIM72) E3-ubiquitin-ligase-mediated AMPKα degradation and deactivation. Specifically, high-glucose-stimulated reactive oxygen species (ROS) signals AKT to phosphorylate AMPKα at S485/491, which facilitates the recruitment of MG53 and the subsequent ubiquitination and degradation of AMPKα. In addition, high glucose deactivates AMPK by ROS-dependent suppression of phosphorylation of AMPKα at T172. These findings not only delineate the mechanism underlying the impairment of AMPK signaling in overnutrition-related diseases but also highlight the significance of keeping the yin-yang balance of AMPK signaling in the maintenance of metabolic homeostasis. |
Persistent Identifier | http://hdl.handle.net/10722/305287 |
ISSN | 2023 Impact Factor: 14.5 2023 SCImago Journal Rankings: 9.332 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Jiang, P | - |
dc.contributor.author | Ren, L | - |
dc.contributor.author | Zhi, L | - |
dc.contributor.author | Yu, Z | - |
dc.contributor.author | Lv, F | - |
dc.contributor.author | Xu, F | - |
dc.contributor.author | Peng, W | - |
dc.contributor.author | Bai, X | - |
dc.contributor.author | Cheng, K | - |
dc.contributor.author | Quan, L | - |
dc.contributor.author | Zhang, X | - |
dc.contributor.author | Wang, X | - |
dc.contributor.author | Zhang, Y | - |
dc.contributor.author | Yang, D | - |
dc.contributor.author | Hu, X | - |
dc.contributor.author | Xiao, RP | - |
dc.date.accessioned | 2021-10-20T10:07:17Z | - |
dc.date.available | 2021-10-20T10:07:17Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Molecular Cell, 2021, v. 81 n. 3, p. 629-637.e5 | - |
dc.identifier.issn | 1097-2765 | - |
dc.identifier.uri | http://hdl.handle.net/10722/305287 | - |
dc.description.abstract | As a master regulator of metabolism, AMP-activated protein kinase (AMPK) is activated upon energy and glucose shortage but suppressed upon overnutrition. Exaggerated negative regulation of AMPK signaling by nutrient overload plays a crucial role in metabolic diseases. However, the mechanism underlying the negative regulation is poorly understood. Here, we demonstrate that high glucose represses AMPK signaling via MG53 (also called TRIM72) E3-ubiquitin-ligase-mediated AMPKα degradation and deactivation. Specifically, high-glucose-stimulated reactive oxygen species (ROS) signals AKT to phosphorylate AMPKα at S485/491, which facilitates the recruitment of MG53 and the subsequent ubiquitination and degradation of AMPKα. In addition, high glucose deactivates AMPK by ROS-dependent suppression of phosphorylation of AMPKα at T172. These findings not only delineate the mechanism underlying the impairment of AMPK signaling in overnutrition-related diseases but also highlight the significance of keeping the yin-yang balance of AMPK signaling in the maintenance of metabolic homeostasis. | - |
dc.language | eng | - |
dc.publisher | Cell Press. The Journal's web site is located at http://www.elsevier.com/locate/molcel | - |
dc.relation.ispartof | Molecular Cell | - |
dc.title | Negative regulation of AMPK signaling by high glucose via E3 ubiquitin ligase MG53 | - |
dc.type | Article | - |
dc.identifier.email | Yang, D: yangdan@hku.hk | - |
dc.identifier.authority | Yang, D=rp00825 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.molcel.2020.12.008 | - |
dc.identifier.pmid | 33400924 | - |
dc.identifier.scopus | eid_2-s2.0-85099693218 | - |
dc.identifier.hkuros | 327913 | - |
dc.identifier.volume | 81 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 629 | - |
dc.identifier.epage | 637.e5 | - |
dc.identifier.isi | WOS:000632641500007 | - |
dc.publisher.place | United States | - |