MKK4 (JNKK1, MAP2K4, and SEK1), a dual-specificity kinase gene on chromosome 17p11, is a tumor suppressor gene that is mutated in a subset of most tumor types. MKK4 protein is activated by several kinases, and active MKK4 cooperates with MKK7 to phosphorylate and thereby activate Jun NH2-terminal kinase (JNK) in the stress-activated cascade. This tumor suppressor gene is distinguished by a remarkably consistent mutational rate across diverse tumor types and an unusually high rate of loss of heterozygosity, has the surprisingly low rate of genetic inactivation of only 5%. Scientists at Johns Hopkins University have engineered a somatic gene knockout of MKK4 in human cancer cells.
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These engineered cancer cell lines which lack MKK4 are useful to screen for chemopreventive or chemotherapeutic agents.
