title: Sumoylation of AMPKβ2 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 α and two regulatory subunits (β and γ). AMPK activity is regulated allosterically by AMP and by the phosphorylation of residue Thr-172 within the catalytic domain of the AMPKα subunit by upstream kinases. We present evidence that the AMPKβ2 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 AMPKβ2 subunit by the attachment of SUMO2 but not SUMO1 moieties. Of interest, AMPKβ1 is not a substrate for this modification. We also demonstrate that sumoylation of AMPKβ2 enhances the activity of the trimeric α2β2γ1 AMPK complex. In addition, our results indicate that sumoylation is antagonist and competes with the ubiquitination of the AMPKβ2 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.
authors.affiliation: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, and Centro de Investigación en Red de Enfermedades Raras, 46010-Valencia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rubio
authors.forename: Santiago
authors.initials: S
authors.lastname: Vernia
authors.forename: Pascual
authors.initials: P
authors.lastname: Sanz
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
chemical_list: D021122:Protein Subunits; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D000249:Adenosine Monophosphate; C526183:PRKAB2 protein, human; D055372:AMP-Activated Protein Kinases
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