Sumoylation of AMPKβ2 subunit enhances AMP-activated protein kinase activity.
Sumoylation of AMPKβ2 subunit enhances AMP-activated protein kinase activity.
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DOI：
10.1091/mbc.e12-11-0806
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发表时间：
2013-06
影响因子：
3.3
通讯作者：
Sanz P
中科院分区：
文献类型：
--
作者：
Rubio T;Vernia S;Sanz P
AMPK β 2亚基可以通过E3-SUMO连接酶PIASy进行的SUMO化修饰，PIASy连接SUMO 2而不是SUMO 1部分。这种翻译后修饰对AMPK β 2具有特异性，并增强AMPK复合物的活性。AMPK β 2的SUMO化是拮抗性的，并与相同亚基的泛素化竞争。AMP活化蛋白激酶（AMPK）是细胞能量状态的传感器。它是由一个催化α亚基和两个调节亚基（β和γ）组成的异源三聚体。AMPK活性受AMP和上游激酶对AMPK α亚基催化结构域内Thr-172残基的磷酸化作用的变构调节。我们提出的证据表明，AMPK β 2亚基可以通过sumoylation后修饰。该过程由活化STAT PIASy的E3-小泛素样修饰物（SUMO）连接酶蛋白抑制剂进行，其通过连接SUMO 2而非SUMO 1部分修饰AMPK β 2亚基。有趣的是，AMPK β 1不是这种修饰的底物。我们还证明AMPK β 2的SUMO化增强了三聚体α 2 β 2 γ 1 AMPK复合物的活性。此外，我们的研究结果表明，SUMO化是拮抗剂，并与AMPK β 2亚基的泛素化竞争。这为AMPK复合物活性的调节增加了一层新的复杂性，因为促进泛素化的条件导致失活，而促进类小泛素化的条件导致AMPK复合物的活化。
The AMPKβ2 subunit can be modified by sumoylation carried out by the E3-SUMO ligase PIASy, which attaches SUMO2 but not SUMO1 moieties. This posttranslational modification is specific to AMPKβ2 and enhances the activity of the AMPK complex. Sumoylation of AMPKβ2 is antagonistic and competes with ubiquitination of the same subunit. 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.