Cloning Major Cancer Players: Researchers Pull Kinases Out Of Their Genomes

'Clone' is an odd term culturally. Thanks to science fiction on one side and ethical hysteria on the other, people tend to overstate the meaning of it. Back before genomes, to 'clone a gene' was to basically discover it - it meant you found the stretch of DNA encoding that gene - but now we know where almost all of the genes are. So 'cloning' in this context does not mean 'discovery' and it certainly doesn't mean Sith Lords spitting out an army of warriors to take over the universe - it means taking known genes (in tiny pieces in the genome) and isolating the spliced versions into a format that can be used in the lab. While a few human genomes have been sequenced, the real work of understanding cancer (and curing it) is still a long way off because most human genes have not been isolated.

'Clone' is an odd term culturally. Thanks to science fiction on one side and ethical hysteria on the other, people tend to overstate the meaning of it.

Back before genomes, to 'clone a gene' was to basically discover it - it meant you found the stretch of DNA encoding that gene - but now we know where almost all of the genes are. So 'cloning' in this context does not mean 'discovery' and it certainly doesn't mean Sith Lords spitting out an army of warriors to take over the universe - it means taking known genes (in tiny pieces in the genome) and isolating the spliced versions into a format that can be used in the lab.

While a few human genomes have been sequenced, the real work of understanding cancer (and curing it) is still a long way off because most human genes have not been isolated.

The protein kinases are the most common class of cancer-associated genes because they mediate the majority of signaling events in cells by phosphorylating and modulating the activity of other proteins.

It has been estimated that up to a quarter of kinases may play a role in human cancers and a group of researchers from the US and Finland say they have made steps toward understanding the mystery by the cloning of nearly all predicted human protein kinase genes in functional form and generation of a corresponding set of kinases lacking catalytic activity that are necessary for functional studies.

They further used the kinome collection in several high-throughput screens, including a screen which identified two novel kinases regulating the Hedgehog signaling pathway – a key pathway linked to multiple types of human cancer. They also say they have identified a novel kinase required for activation of Kaposi’s sarcoma herpesvirus.

“The isolated kinase genes form a resource that scientists can now use to systematically map kinase signaling networks in different cellular disease models. The kinases are also promising targets for therapeutic intervention in the treatment of various cancers,” states Professor Jussi Taipale from the National Public Health Institute and University of Helsinki.

The study was financially supported by the Finnish Academy Centre of Excellence for Translational Genome-Scale Biology, the European Union FP6 Tumorhost genomics and INCA -projects, Biocentrum Helsinki, University of Helsinki, The Sigrid Juselius Foundation, The Emil Aaltonen Foundation, The Finnish Cultural Foundation, The Maud Kuistila Memorial Foundation and the Finnish Cancer Organisations.

Article: Markku Varjosalo, Mikael Björklund, Fang Cheng, Heidi Syvänen, Teemu Kivioja, Sami Kilpinen, Zairen Sun, Olli Kallioniemi, Hendrik G. Stunnenberg, Wei-Wu He, Päivi Ojala, and Jussi Taipale. Application of active and kinase-deficient kinome collection for identification of kinases regulating Hedgehog signaling, Cell, Vol 133, 537-548, 02 May 2008.

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