Superoxide dismutase is regulated by LAMMER kinase in Drosophila and human cells.

Superoxide dismutase is regulated by LAMMER kinase in Drosophila and human cells.
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DOI:
10.1016/j.freeradbiomed.2008.12.012
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发表时间:
2009-03-15
影响因子:
7.4
通讯作者:
Powis, Garth
Powis, Garth
中科院分区:
医学1区
文献类型:
--
作者:
James, Brian P.;Staatz, William D.;Wilkinson, Sarah T.;Meuillet, Emmanuelle;Powis, Garth

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LAMMER激酶(也称为Cdc - 2样激酶或CLKs)是一个双特异性丝氨酸/苏氨酸蛋白激酶家族,存在于所有已测序的真核生物基因组中。在裂殖酵母粟酒裂殖酵母中,LAMMER激酶基因Lkh1正向调节抗氧化防御基因超氧化物歧化酶1(sod1 +,CuZn - SOD)和过氧化氢酶(ctt1 +,CAT)的表达。我们已经表明,果蝇LAMMER激酶基因杏色减弱子(Doa)的突变可防止由活性氧(ROS)产生剂百草枯导致的寿命缩短,同时细胞质(CuZn - Sod或SOD1)和线粒体超氧化物歧化酶(Mn - Sod或SOD2)的蛋白质水平和活性增加。在HeLa和MCF - 7人类细胞系中,通过小干扰RNA(siRNA)介导的人类LAMMER激酶基因CLK - 1的敲低导致SOD1活性和mRNA转录水平均增加。这些数据表明,在果蝇和人类细胞系中,SOD1受到LAMMER激酶的负调控,并且这种调控在进化过程中可能是保守的。
LAMMER kinases (also know as Cdc-2-like or CLKs) are a family of dual specificity serine/threonine protein kinases that are found in all sequenced eukaryotic genomes. In the fission yeast, S. pombe, the LAMMER kinase gene, Lkh1, positively regulates the expression of the antioxidant defense genes, superoxide dismutase1 (sod1+, CuZn-SOD) and catalase (ctt1+, CAT). We have shown that mutations in the Drosophila LAMMER kinase gene, Darkener of apricot (Doa), protect against the decrease in life span caused by the reactive oxygen species (ROS) generator paraquat, and at the same time show an increase in cytoplasmic (CuZn-Sod or SOD1) and mitochondrial superoxide dismutase (Mn-Sod or SOD2) protein levels and activity. The siRNA mediated knock down of the human LAMMER kinase gene, CLK-1, in HeLa and MCF-7 human cell lines leads to an increase in both SOD1 activity and mRNA transcript levels. These data suggest that SOD1 is negatively regulated by LAMMER kinases in Drosophila and human cell lines and that this regulation may be conserved during evolution.
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