Human CLK2 links cell cycle progression, apoptosis, and telomere length regulation.
Mutations in the clk-2 gene of the nematode Caenorhabditis elegans affect organismal features such as development, behavior, reproduction, and aging as well as cellular features such as the cell cycle, apoptosis, the DNA replication checkpoint, and telomere length. clk-2 encodes a novel protein (CLK-2) with a unique homologue in each of the sequenced eukaryotic genomes. We have studied the human homologue of CLK-2 (hCLK2) to determine whether it affects the same set of cellular features as CLK-2. We find that overexpression of hCLK2 decreases cell cycle length and that inhibition of hCLK2 expression arrests the cell cycle reversibly. Overexpression of hCLK2, however, renders the cell hypersensitive to apoptosis triggered by oxidative stress or DNA replication block and gradually increases telomere length. The evolutionary conservation of the pattern of cellular functions affected by CLK-2 suggests that the function of hCLK2 in humans might also affect the same organismal features as in worms, including life span. Surprisingly, we find that hCLK2 is present in all cellular compartments and exists as a membrane-associated as well as a soluble form.
Jiang
Ning
N
Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada.
Bénard
Claire Y
CY
Kébir
Hania
H
Shoubridge
Eric A
EA
Hekimi
Siegfried
S
D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D018384:Oxidative Stress; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D013997:Time Factors
D018076:DNA, Complementary; D034741:RNA, Small Interfering; D008156:Luciferases; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases