SAM Pointed domain of ETS-2 subfamily of ETS transcriptional regulators is a protein-protein interaction domain. It contains a docking site for Cdk10 (cyclin-dependent kinase 10), a member of the Cdc2 kinase family. The interaction between ETS-2 and Cdk10 kinase inhibits ETS-2 transactivation activity in mammals. ETS-2 is also regulated by ERK2 MAP kinase. ETS-2, which is phosphorylated by ERK2, can interact with coactivators and enhance transactivation. ETS-2 transcriptional activators are involved in embryonic development and cell cycle control. The Ets-2 gene is a proto-oncogene. It is overexpressed in breast and prostate cancer cells and its overexpression is necessary for transformation of such cells. Members of ETS-2 subfamily are potential molecular targets for selective cancer therapy.
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