TY - JOUR
T1 - A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress
AU - Ritho, Joan
AU - Arold, Stefan T.
AU - Yeh, Edward T.H.
N1 - KAUST Repository Item: Exported on 2020-10-01
PY - 2015/7/23
Y1 - 2015/7/23
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/561186
UR - http://linkinghub.elsevier.com/retrieve/pii/S2211124715007287
UR - http://www.scopus.com/inward/record.url?scp=84938552420&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.07.002
DO - 10.1016/j.celrep.2015.07.002
M3 - Article
C2 - 26212320
SN - 2211-1247
VL - 12
SP - 734
EP - 742
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -