Department of Cardiovascular Medicine, University of Oxford, West Wing Level 6, John Radcliffe Hospital, Oxford, United Kingdom.
Cell Cycle. 2012 Mar 1;11(5):917-21. doi: 10.4161/cc.11.5.19412.
AMP-activated protein kinase has been shown to be a key regulator of energy homeostasis; it has also been identified as a tumor suppressor and is required for correct cell division and chromosome segregation during mitosis. The enzyme is a heterotrimer, with each subunit having more than one isoform, each encoded by a separate gene (two α, two β and three γ isoforms). In human endothelial cells, the activated kinase subunit of AMPK in the cytokinetic apparatus is α2, the minority α subunit, which co-localizes with β2 and γ2. This is the first demonstration of a trimeric complex of AMPK containing the γ2 regulatory subunit becoming selectively activated and being linked to mitotic processes. We also show that α1 and γ1, the predominant AMPK subunits, are almost exclusively localized in the cytoskeleton, while α2 and γ2 are present in all subcellular fractions, including the nuclei. These data suggest that pharmacological interventions targeted to specific AMPK subunit isoforms have the potential to modify selective functions of AMPK.
AMP 激活的蛋白激酶已被证明是能量平衡的关键调节因子；它也被确定为肿瘤抑制因子，是有丝分裂过程中正确的细胞分裂和染色体分离所必需的。该酶是一种异三聚体，每个亚基都有一个以上的同工型，每个同工型都由一个单独的基因编码（两个α、两个β和三个γ同工型）。在人内皮细胞中，胞质分裂装置中 AMPK 的激活激酶亚基是α2，即少数的α亚基，它与β2和γ2共定位。这是第一个证明包含γ2 调节亚基的 AMPK 三聚体复合物被选择性激活并与有丝分裂过程相关的例证。我们还表明，α1 和γ1，即 AMPK 的主要亚基，几乎完全定位于细胞骨架中，而α2 和γ2 则存在于所有亚细胞部分，包括细胞核。这些数据表明，针对特定 AMPK 亚基同工型的药理学干预有可能改变 AMPK 的选择性功能。
