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 language | English (US) |
---|---|
Pages (from-to) | 734-742 |
Number of pages | 9 |
Journal | Cell Reports |
Volume | 12 |
Issue number | 5 |
DOIs | |
State | Published - Jul 23 2015 |
Bibliographical note
KAUST Repository Item: Exported on 2020-10-01ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology