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

J. Ritho, S.T. Arold, E.T. Yeh
Cell Rep, 12(5), pp. 734-742, (2015)

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

Keywords

SUMO1 Modification, LKB1 Regulates, AMPK Activity

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.

Code

DOI: 10.1016/j.celrep.2015.07.002

Sources

Website PDF

See all publications 2015