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Gene Review

Mapk8ip1  -  mitogen-activated protein kinase 8...

Mus musculus

Synonyms: C-Jun-amino-terminal kinase-interacting protein 1, IB-1, IB1, Ib1, Islet-brain-1, ...
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Disease relevance of Mapk8ip1

  • Increased vulnerability to kainic acid-induced epileptic seizures in mice underexpressing the scaffold protein Islet-Brain 1/JIP-1 [1].
  • These data identify JIP1 as a novel molecular target for therapeutic intervention in the development of obesity [2].
  • Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease [3].
  • In the cultures, ischemia reduced JIP1 expression and activated JNK, c-Jun, and caspase 3 [4].
  • Antibody IB1 reacted with 3 of 13 hepatoma tissues, but with none of the normal liver and other tissues, and antibody 9B2 was reactive with antigens appearing on the bile canalicular domain of hepatoma and normal liver tissues [5].

Psychiatry related information on Mapk8ip1


High impact information on Mapk8ip1


Biological context of Mapk8ip1


Anatomical context of Mapk8ip1


Associations of Mapk8ip1 with chemical compounds

  • Both ALLN and lactacystin caused a marked decrease in the cellular amount of the JNK scaffold protein JNK-interacting protein 1/islet-brain-1 [16].
  • In contrast, another group (Whitmarsh et al. [2001] Genes Dev. 15:2421-2432) demonstrated that JIP1-deficient mice were viable and that the JIP1 null mutation inhibited the kainic acid-induced JNK activation and neuronal death [17].
  • Last, the REST-mediated repression of IB1 could be abolished by trichostatin A, indicating that deacetylase activity is required to allow REST repression [18].
  • Islet-brain1 (IB1) or c-Jun NH2 terminal kinase interacting protein-1 (JIP-1), the product of the MAPK8IP1 gene, functions as a neuronal scaffold protein to allow signalling specificity [6].

Physical interactions of Mapk8ip1

  • Components of the JNK signaling pathway interact with the JIP1 scaffold protein [8].

Enzymatic interactions of Mapk8ip1

  • These results suggest that JIP1 plays a pivotal role in regulating the maintenance of phosphorylated JNK and neuronal survival in postischemic brain, but is not essential for JNK activation and early development [17].

Regulatory relationships of Mapk8ip1


Other interactions of Mapk8ip1

  • Subsequently, an increasing activation of JNK in the 8 h following seizure induction was observed in IB1/JIP-1 haploinsufficient mice, which also underwent more severe excitotoxic lesions in hippocampal CA3, as assessed histologically 3 days after KA administration [1].
  • The association is specific to JIP3, as the two other JIPs, JIP1 and JIP2, failed to bind TLR4 [20].
  • Targeted disruption of the gene MAPK8IP1 encoding IB1/JIP-1 in mice led to embryonic death prior to blastocyst implantation [12].
  • This pattern was consistent through different litters, which suggests that the up- or down-regulation of JIP-1 may well be part of the intracellular mediation of IGF II induced messages [21].
  • Repression of phospho-JNK and infarct volume in ischemic brain of JIP1-deficient mice [17].

Analytical, diagnostic and therapeutic context of Mapk8ip1


  1. Increased vulnerability to kainic acid-induced epileptic seizures in mice underexpressing the scaffold protein Islet-Brain 1/JIP-1. Magara, F., Haefliger, J.A., Thompson, N., Riederer, B., Welker, E., Nicod, P., Waeber, G. Eur. J. Neurosci. (2003) [Pubmed]
  2. An essential role of the JIP1 scaffold protein for JNK activation in adipose tissue. Jaeschke, A., Czech, M.P., Davis, R.J. Genes Dev. (2004) [Pubmed]
  3. Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease. Xia, X.G., Harding, T., Weller, M., Bieneman, A., Uney, J.B., Schulz, J.B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. JIP1 regulates neuronal apoptosis in response to stress. Dong, Z., Zhou, L., Del Villar, K., Ghanevati, M., Tashjian, V., Miller, C.A. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  5. Monoclonal antibodies against antigens expressed on human hepatocellular carcinoma cells. Hu, C.P., Han, S.H., Lui, W.Y., Hsu, H.C., Lin, Y.M., Lin, P.H., Chen, L.R., Hsieh, H.G., Kuo, P.T., P'eng, F.K. Hepatology (1986) [Pubmed]
  6. Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease. Helbecque, N., Abderrahamani, A., Meylan, L., Riederer, B., Mooser, V., Miklossy, J., Delplanque, J., Boutin, P., Nicod, P., Haefliger, J.A., Cottel, D., Amouyel, P., Froguel, P., Waeber, G., Abderrhamani, A. Mol. Psychiatry (2003) [Pubmed]
  7. A cytoplasmic inhibitor of the JNK signal transduction pathway. Dickens, M., Rogers, J.S., Cavanagh, J., Raitano, A., Xia, Z., Halpern, J.R., Greenberg, M.E., Sawyers, C.L., Davis, R.J. Science (1997) [Pubmed]
  8. Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Whitmarsh, A.J., Kuan, C.Y., Kennedy, N.J., Kelkar, N., Haydar, T.F., Mordes, J.P., Appel, M., Rossini, A.A., Jones, S.N., Flavell, R.A., Rakic, P., Davis, R.J. Genes Dev. (2001) [Pubmed]
  9. Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1. Muresan, Z., Muresan, V. J. Cell Biol. (2005) [Pubmed]
  10. Notch interferes with the scaffold function of JNK-interacting protein 1 to inhibit the JNK signaling pathway. Kim, J.W., Kim, M.J., Kim, K.J., Yun, H.J., Chae, J.S., Hwang, S.G., Chang, T.S., Park, H.S., Lee, K.W., Han, P.L., Cho, S.G., Kim, T.W., Choi, E.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  11. alpha-Synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in neuronal cells. Hashimoto, M., Hsu, L.J., Rockenstein, E., Takenouchi, T., Mallory, M., Masliah, E. J. Biol. Chem. (2002) [Pubmed]
  12. Islet-brain1/JNK-interacting protein-1 is required for early embryogenesis in mice. Thompson, N.A., Haefliger, J.A., Senn, A., Tawadros, T., Magara, F., Ledermann, B., Nicod, P., Waeber, G. J. Biol. Chem. (2001) [Pubmed]
  13. The scaffold protein IB1/JIP-1 controls the activation of JNK in rat stressed urothelium. Tawadros, T., Formenton, A., Dudler, J., Thompson, N., Nicod, P., Leisinger, H.J., Waeber, G., Haefliger, J.A. J. Cell. Sci. (2002) [Pubmed]
  14. The axon guidance defect of the telencephalic commissures of the JSAP1-deficient brain was partially rescued by the transgenic expression of JIP1. Ha, H.Y., Cho, I.H., Lee, K.W., Lee, K.W., Song, J.Y., Kim, K.S., Yu, Y.M., Lee, J.K., Song, J.S., Yang, S.D., Shin, H.S., Han, P.L. Dev. Biol. (2005) [Pubmed]
  15. Spatial, temporal and subcellular localization of islet-brain 1 (IB1), a homologue of JIP-1, in mouse brain. Pellet, J.B., Haefliger, J.A., Staple, J.K., Widmann, C., Welker, E., Hirling, H., Bonny, C., Nicod, P., Catsicas, S., Waeber, G., Riederer, B.M. Eur. J. Neurosci. (2000) [Pubmed]
  16. Antitumorigenic effect of proteasome inhibitors on insulinoma cells. Størling, J., Allaman-Pillet, N., Karlsen, A.E., Billestrup, N., Bonny, C., Mandrup-Poulsen, T. Endocrinology (2005) [Pubmed]
  17. Repression of phospho-JNK and infarct volume in ischemic brain of JIP1-deficient mice. Im, J.Y., Lee, K.W., Kim, M.H., Lee, S.H., Ha, H.Y., Cho, I.H., Kim, D., Yu, M.S., Kim, J.B., Lee, J.K., Kim, Y.J., Youn, B.W., Yang, S.D., Shin, H.S., Han, P.L. J. Neurosci. Res. (2003) [Pubmed]
  18. The transcriptional repressor REST determines the cell-specific expression of the human MAPK8IP1 gene encoding IB1 (JIP-1). Abderrahmani, A., Steinmann, M., Plaisance, V., Niederhauser, G., Haefliger, J.A., Mooser, V., Bonny, C., Nicod, P., Waeber, G. Mol. Cell. Biol. (2001) [Pubmed]
  19. Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death. Parkinson, D.B., Bhaskaran, A., Droggiti, A., Dickinson, S., D'Antonio, M., Mirsky, R., Jessen, K.R. J. Cell Biol. (2004) [Pubmed]
  20. JNK-interacting protein 3 associates with Toll-like receptor 4 and is involved in LPS-mediated JNK activation. Matsuguchi, T., Masuda, A., Sugimoto, K., Nagai, Y., Yoshikai, Y. EMBO J. (2003) [Pubmed]
  21. Expression of JNK interacting protein JIP-1 is down-regulated in liver from mouse embryos with a disrupted insulin-like growth factor II gene. Rohbe, L., Larsson, M., Rising, A., Grip, S., Burns, J., Engström, W. In Vivo (2004) [Pubmed]
  22. Interaction of c-Jun amino-terminal kinase interacting protein-1 with p190 rhoGEF and its localization in differentiated neurons. Meyer, D., Liu, A., Margolis, B. J. Biol. Chem. (1999) [Pubmed]
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