Sumoylation of AMPK?2 subunit enhances AMP-activated protein kinase activity.

ABSTRACT: AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is a heterotrimer composed of a catalytic ? and two regulatory subunits (? and ?). AMPK activity is regulated allosterically by AMP and by the phosphorylation of residue Thr-172 within the catalytic domain of the AMPK? subunit by upstream kinases. We present evidence that the AMPK?2 subunit may be posttranslationally modified by sumoylation. This process is carried out by the E3-small ubiquitin-like modifier (SUMO) ligase protein inhibitor of activated STAT PIASy, which modifies the AMPK?2 subunit by the attachment of SUMO2 but not SUMO1 moieties. Of interest, AMPK?1 is not a substrate for this modification. We also demonstrate that sumoylation of AMPK?2 enhances the activity of the trimeric ?2?2?1 AMPK complex. In addition, our results indicate that sumoylation is antagonist and competes with the ubiquitination of the AMPK?2 subunit. This adds a new layer of complexity to the regulation of the activity of the AMPK complex, since conditions that promote ubiquitination result in inactivation, whereas those that promote sumoylation result in the activation of the AMPK complex.

SUBMITTER: Rubio T 

PROVIDER: S-EPMC3667731 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature