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

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Ritho J,Arold ST,Yeh ET

doi

10.1016/j.celrep.2015.07.002

subject

Has Abstract

pub_date

2015-08-04 00:00:00

pages

734-42

issue

5

issn

2211-1247

pii

S2211-1247(15)00728-7

journal_volume

12

pub_type

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