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Gene Review

Mapk8ip1  -  mitogen-activated protein kinase 8...

Rattus norvegicus

Synonyms: C-Jun-amino-terminal kinase-interacting protein 1, IB-1, Ib1, Islet-brain-1, JIP-1, ...
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Disease relevance of Mapk8ip

  • Akt1 binding to JIP-1 acts as a regulatory gate preventing JNK activation, which is opened under conditions ischemia injury [1].
  • These results point towards PIN and JIP-1 as antiapoptotic factors contributing to selective resistance of granule cells, whereas Caspase-3 may be involved in cell death of hippocampal CA1, CA3 and hilar neurons in the kainate epilepsy model [2].
  • A neuroprotective protein, JNK-interacting protein 1 (JIP1), an inhibitor of JNK-mediated apoptosis, was reduced by 6-h hypoxia and markedly decreased by 24-h reoxygenation in CA1 neurons as was DENN/MADD, which also modulates JNK-mediated cell death [3].
  • Here, we show that JNK activation is essential for alpha(1)AR-induced hypertrophy, in that alpha(1)AR-induced hypertrophic responses, such as reorganization of the actin cytoskeleton and increased protein synthesis, could be blocked by expressing the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of JNK [4].

High impact information on Mapk8ip

  • Overexpression of Akt1 mutants that bind JIP1 reduced excitotoxic apoptosis [5].
  • IB1 is expressed at high levels in neurons and in pancreatic beta-cells, where it controls expression of several insulin-secretory components and secretion [6].
  • Taken together, these results indicate that IB1 homodimerization through its SH3 domain has pleiotropic effects including regulation of the insulin secretion process [6].
  • IB1 has been shown to homodimerize, but neither the molecular mechanisms nor the function of dimerization have yet been characterized [6].
  • The highly stable IB1 homodimer can be significantly destabilized in vitro by three individual point mutations directed against key residues involved in dimerization [6].

Chemical compound and disease context of Mapk8ip


Biological context of Mapk8ip


Anatomical context of Mapk8ip


Associations of Mapk8ip with chemical compounds


Physical interactions of Mapk8ip


Other interactions of Mapk8ip

  • Together, these facts point to a central role of the IB1/JIP-1 protein in the control of TRH-mediated TSH-beta stimulation [7].

Analytical, diagnostic and therapeutic context of Mapk8ip


  1. Involvement of oxidative stress in the rapid Akt1 regulating a JNK scaffold during ischemia in rat hippocampus. Pan, J., Pei, D.S., Yin, X.H., Hui, L., Zhang, G.Y. Neurosci. Lett. (2006) [Pubmed]
  2. Differential regulation of apoptosis-related genes in resistant and vulnerable subfields of the rat epileptic hippocampus. Becker, A.J., Gillardon, F., Blümcke, I., Langendörfer, D., Beck, H., Wiestler, O.D. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  3. Neurogenesis response to hypoxia-induced cell death: map kinase signal transduction mechanisms. Zhou, L., Del Villar, K., Dong, Z., Miller, C.A. Brain Res. (2004) [Pubmed]
  4. Galpha(12/13) mediates alpha(1)-adrenergic receptor-induced cardiac hypertrophy. Maruyama, Y., Nishida, M., Sugimoto, Y., Tanabe, S., Turner, J.H., Kozasa, T., Wada, T., Nagao, T., Kurose, H. Circ. Res. (2002) [Pubmed]
  5. Akt1 regulates a JNK scaffold during excitotoxic apoptosis. Kim, A.H., Yano, H., Cho, H., Meyer, D., Monks, B., Margolis, B., Birnbaum, M.J., Chao, M.V. Neuron (2002) [Pubmed]
  6. A unique set of SH3-SH3 interactions controls IB1 homodimerization. Kristensen, O., Guenat, S., Dar, I., Allaman-Pillet, N., Abderrahmani, A., Ferdaoussi, M., Roduit, R., Maurer, F., Beckmann, J.S., Kastrup, J.S., Gajhede, M., Bonny, C. EMBO J. (2006) [Pubmed]
  7. Thyrotropin-releasing hormone-stimulated thyrotropin expression involves islet-brain-1/c-Jun N-terminal kinase interacting protein-1. Abe, H., Murao, K., Imachi, H., Cao, W.M., Yu, X., Yoshida, K., Wong, N.C., Shupnik, M.A., Haefliger, J.A., Waeber, G., Ishida, T. Endocrinology (2004) [Pubmed]
  8. IB1, a JIP-1-related nuclear protein present in insulin-secreting cells. Bonny, C., Nicod, P., Waeber, G. J. Biol. Chem. (1998) [Pubmed]
  9. Inhibition of JNK by overexpression of the JNL binding domain of JIP-1 prevents apoptosis in sympathetic neurons. Harding, T.C., Xue, L., Bienemann, A., Haywood, D., Dickens, M., Tolkovsky, A.M., Uney, J.B. J. Biol. Chem. (2001) [Pubmed]
  10. Increased JNK phosphorylation and oxidative stress in response to increased glucose flux through increased GLUT1 expression in rat retinal endothelial cells. Zhou, J., Deo, B.K., Hosoya, K., Terasaki, T., Obrosova, I.G., Brosius, F.C., Kumagai, A.K. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  11. c-Jun N-terminal kinase-interacting protein 1 inhibits gene expression in response to hypertrophic agonists in neonatal rat ventricular myocytes. Finn, S.G., Dickens, M., Fuller, S.J. Biochem. J. (2001) [Pubmed]
  12. Molecular cloning of multiple splicing variants of JIP-1 preferentially expressed in brain. Kim, I.J., Lee, K.W., Park, B.Y., Lee, J.K., Park, J., Choi, I.Y., Eom, S.J., Chang, T.S., Kim, M.J., Yeom, Y.I., Chang, S.K., Lee, Y.D., Choi, E.J., Han, P.L. J. Neurochem. (1999) [Pubmed]
  13. Activated mitogen-activated protein kinase kinase 7 redistributes to the cytosol and binds to Jun N-terminal kinase-interacting protein 1 involving oxidative stress during early reperfusion in rat hippocampal CA1 region. Li, C.H., Wang, R.M., Zhang, Q.G., Zhang, G.Y. J. Neurochem. (2005) [Pubmed]
  14. Up-regulation of genes involved in cellular stress and apoptosis in a rat model of hippocampal degeneration. Anguelova, E., Boularand, S., Nowicki, J.P., Benavides, J., Smirnova, T. J. Neurosci. Res. (2000) [Pubmed]
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