A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress

Handle URI:
http://hdl.handle.net/10754/561186
Title:
A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress
Authors:
Ritho, Joan; Arold, Stefan T. ( 0000-0001-5278-0668 ) ; Yeh, Edward T.H.
Abstract:
SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell’s energy equilibrium.
KAUST Department:
Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress 2015 Cell Reports
Journal:
Cell Reports
Issue Date:
23-Jul-2015
DOI:
10.1016/j.celrep.2015.07.002
Type:
Article
ISSN:
22111247
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S2211124715007287
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorRitho, Joanen
dc.contributor.authorArold, Stefan T.en
dc.contributor.authorYeh, Edward T.H.en
dc.date.accessioned2015-07-28T13:02:51Zen
dc.date.available2015-07-28T13:02:51Zen
dc.date.issued2015-07-23en
dc.identifier.citationA Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress 2015 Cell Reportsen
dc.identifier.issn22111247en
dc.identifier.doi10.1016/j.celrep.2015.07.002en
dc.identifier.urihttp://hdl.handle.net/10754/561186en
dc.description.abstractSUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell’s energy equilibrium.en
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S2211124715007287en
dc.rightsArchived with thanks to Cell Reports. Under a Creative Commons license, http://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.titleA Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stressen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalCell Reportsen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAen
dc.contributor.institutionCancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USAen
kaust.authorArold, Stefan T.en
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