tg-003 and Aging--Premature

LAMMER kinases (also known 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, Schizosaccharomyces pombe, the LAMMER kinase gene, Lkh1, positively regulates the expression of the antioxidant defense genes, superoxide dismutase 1 (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.

Topics: Aging, Premature; Animals; Drosophila melanogaster; Drosophila Proteins; Enzyme Activation; Gene Expression Regulation; HeLa Cells; Humans; Mutation; Oxidative Stress; Paraquat; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; RNA, Small Interfering; Superoxide Dismutase; Superoxide Dismutase-1; Survival Analysis; Thiazoles