Scientific background: |
MAP2K7(Mitogen-activated protein kinase kinase 7), also known as MAP kinase kinase 7, MAPKK7, JNKK2, PRKMK7 or MKK7, is an enzyme that in humans is encoded by the MAP2K7 gene. This protein is a member of the mitogen-activated protein kinase kinase family. The MKK7 protein exists as six different isoforms with three possible N-termini (alpha, beta, and gamma isoforms) and two possible C-termini (1 and 2 isoforms). Schramek et al. (2011) showed that the doxorubicin-mediated DNA damage response in human A549 lung carcinoma cells caused rapid phosphorylation and upregulation of p53 (TP53). MKK7 knockdown reduced p53 phosphorylation, delayed p53 upregulation, and interfered with cell cycle arrest at G2/M. MKK7 was activated in primary lung tumors, and tumors with a p53 mutation showed even higher MKK7 phosphorylation. Schramek et al. (2011) concluded that MKK7 exerts its tumor suppressive function through p53. |
References: |
1. Lu, X., Nemoto, S., Lin, A. Identification of c-jun NH(2)-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38. J. Biol. Chem. 272: 24751-24754, 1997.
2. Schramek, D., Kotsinas, A., Meixner, A., Wada, T., Elling, U., Pospisilik, J. A., Neely, G. G., Zwick, R.-H., Sigl, V., Forni, G., Serrano, M., Gorgoulis, V. G., Penninger, J. M. The stress kinase MKK7 couples oncogenic stress to p53 stability and tumor suppression. Nature Genet. 43: 212-219, 2011.
3. Wu, Z., Wu, J., Jacinto, E., Karin, M. Molecular cloning and characterization of human JNKK2, a novel jun NH(2)-terminal kinase-specific kinase. Molec. Cell. Biol. 17: 7407-7416, 1997.
|