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

Joan Ritho, Stefan T. Arold, Edward T.H. Yeh

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)734-742
Number of pages9
JournalCell Reports
Volume12
Issue number5
DOIs
StatePublished - Jul 23 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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