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Gene Review

MAPK8IP1  -  mitogen-activated protein kinase 8...

Homo sapiens

Synonyms: C-Jun-amino-terminal kinase-interacting protein 1, IB-1, IB1, Islet-brain 1, JIP-1, ...
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Disease relevance of MAPK8IP1

  • We evaluated the role of IBi in beta-cells by expression of a MAPK8IP1 antisense RNA in a stable insulinoma beta-cell line [1].
  • Identification of this novel non-maturity onset diabetes of the young (MODY) form of diabetes demonstrates that IB1 is a key regulator of 3-cell function [1].
  • JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0-tetradecanoylphorbol-13-acetate (TPA) [2].
  • (see p. 11 of this issue) report that either binding of the cargo linker c-Jun N-terminal kinase-interacting protein 1 (JIP1) to the light chains (LCs) or binding of fasciculation and elongation protein zeta1 (FEZ1) to the heavy chains (HCs) is insufficient for activation but that activation occurs when both are present simultaneously [3].
  • Vaccinia virus B1R kinase interacts with JIP1 and modulates c-Jun-dependent signaling [4].

High impact information on MAPK8IP1

  • A 38% decrease in IB1 protein content resulted in a 49% and a 41% reduction in SLC2A2 and INS (encoding insulin) mRNA expression, respectively [1].
  • In addition, we detected MAPK8IP1 transcripts and IBi protein in human pancreatic islets [1].
  • We did, however, identify in one family a missense mutation located in the coding region of MAPK8IP1 (559N) that segregated with diabetes [1].
  • METHODS: We studied primary tumours and 156 lymph nodes from 32 patients with cervical cancer (stage IA2, IB1, and IB2) and 32 lymph nodes from nine patients with benign disease [5].
  • In this study, we show that binding of the c-Jun N-terminal kinase-interacting protein 1 (JIP1) cargo protein is not sufficient to activate Kinesin-1 [6].

Biological context of MAPK8IP1

  • We surprisingly found that although JIP-1 can facilitate this phosphorylation, it is not required for this process [7].
  • To identify binding targets for the hJIP-1 PTB domain, a mouse embryo cDNA library was screened using the yeast two-hybrid system [8].
  • Conversely, IB1/JIP-1 overexpression using a viral gene transfer prevented the JNK activation and the 4-HPR-induced apoptosis was blunted [9].
  • Together, these results indicated that IB1/JIP-1 participates to the neuronal phenotype of the human LNCaP cells and is a regulator of JNK signaling pathway [9].
  • Consistent with this hypothesis, we provided evidence that LZK is associated with the C-terminal region of JIP-1 through its kinase catalytic domain [10].

Anatomical context of MAPK8IP1


Associations of MAPK8IP1 with chemical compounds

  • The phosphotyrosine binding domain of JIP1 binds the cytoplasmic tail of AbetaPP, whereas the JIP1 C-terminal region interacts with the tetratrico-peptide repeats of Klc1 [15].
  • Here we have investigated the possibility that JIP1 may also affect the catalytic activity of Akt1, a serine/threonine kinase that has been implicated in multiple cellular processes, including survival and proliferation [16].
  • In the present study, we reveal that two scaffolding proteins, JIP1 and JIP3, have a cross-talk that leads to the regulation of the ASK1-SEK1-JNK signal during glucose deprivation [17].
  • Variations in IB1/JIP1 expression regulate susceptibility of beta-cells to cytokine-induced apoptosis irrespective of C-Jun NH2-terminal kinase signaling [18].
  • PATIENTS AND METHODS: Sixteen pts (group I), FIGO stage IB1 (1), IB2 (4), IIB (10), IIIB (1), received external beam radiotherapy (EBT) with a total dose of 45 Gy in 5 weeks and concomitant CISPLATIN 40 mg/m(2) weekly, followed by BT up to a total dose of 15 Gy [19].

Physical interactions of MAPK8IP1

  • Altogether, our data demonstrate that Akt1 participates in a negative regulatory feedback loop by interacting with the JIP1 scaffold protein [20].
  • However, the corresponding region of JNK bound by this JIP-1-based peptide was unknown [21].
  • Phosphorylated JNK2 binds to JIP1, and the phosphorylation of the Thr-183 residue of JNK2 occurs [17].

Regulatory relationships of MAPK8IP1

  • JNK-interacting protein 1 promotes Akt1 activation [16].
  • IB1/JIP-1 controls JNK activation and increased during prostatic LNCaP cells neuroendocrine differentiation [9].
  • Recent evidence suggests that the JIP-1 gene is co-regulated with the insulin like growth factor II (IGF II) gene, thereby contributing to the growth-promoting effects of this potent growth factor [22].

Other interactions of MAPK8IP1


Analytical, diagnostic and therapeutic context of MAPK8IP1

  • By immobilized metal affinity chromatography and a combined microcapillary LC/MALDI-TOF/ESI-ion trap mass spectrometry approach, we identified 35 sites of mitotic phosphorylation within JIP1, among which eight were present within (Ser/Thr)-Pro sequence [24].
  • Furthermore, in IB1 patients that did not have indications for adjuvant radiotherapy, 15% of patients with elevated preoperative serum SCC-ag levels recurred within 2 years, compared with 1.6% of patients with normal serum SCC-ag levels (P = .02) [25].
  • Patients with early-stage cervical cancer (stages IA and IB1, 23 patients) underwent complete laparoscopic pelvic lymphadenectomy after the SN procedure [26].
  • The 10-year disease-free survival (DFS) rate was 88% for Stage IB1, 44% for Stage IB2, 65% for Stage IIA, and 48% for Stage IIB [27].
  • A comparison of stages IB1 and IB2 cervical cancers treated with radical hysterectomy. Is size the real difference [28]?


  1. The gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes. Waeber, G., Delplanque, J., Bonny, C., Mooser, V., Steinmann, M., Widmann, C., Maillard, A., Miklossy, J., Dina, C., Hani, E.H., Vionnet, N., Nicod, P., Boutin, P., Froguel, P. Nat. Genet. (2000) [Pubmed]
  2. JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0-tetradecanoylphorbol-13-acetate (TPA). Ikezoe, T., Yang, Y., Taguchi, H., Koeffler, H.P. Br. J. Cancer (2004) [Pubmed]
  3. Jump-starting kinesin. Hackney, D.D. J. Cell Biol. (2007) [Pubmed]
  4. Vaccinia virus B1R kinase interacts with JIP1 and modulates c-Jun-dependent signaling. Santos, C.R., Blanco, S., Sevilla, A., Lazo, P.A. J. Virol. (2006) [Pubmed]
  5. Molecular quantification and mapping of lymph-node micrometastases in cervical cancer. Van Trappen, P.O., Gyselman, V.G., Lowe, D.G., Ryan, A., Oram, D.H., Bosze, P., Weekes, A.R., Shepherd, J.H., Dorudi, S., Bustin, S.A., Jacobs, I.J. Lancet (2001) [Pubmed]
  6. Two binding partners cooperate to activate the molecular motor Kinesin-1. Blasius, T.L., Cai, D., Jih, G.T., Toret, C.P., Verhey, K.J. J. Cell Biol. (2007) [Pubmed]
  7. Amyloid beta protein precursor is phosphorylated by JNK-1 independent of, yet facilitated by, JNK-interacting protein (JIP)-1. Scheinfeld, M.H., Ghersi, E., Davies, P., D'Adamio, L. J. Biol. Chem. (2003) [Pubmed]
  8. 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]
  9. IB1/JIP-1 controls JNK activation and increased during prostatic LNCaP cells neuroendocrine differentiation. Tawadros, T., Martin, D., Abderrahmani, A., Leisinger, H.J., Waeber, G., Haefliger, J.A. Cell. Signal. (2005) [Pubmed]
  10. Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway. Ikeda, A., Hasegawa, K., Masaki, M., Moriguchi, T., Nishida, E., Kozutsumi, Y., Oka, S., Kawasaki, T. J. Biochem. (2001) [Pubmed]
  11. cDNA cloning and mapping of a novel islet-brain/JNK-interacting protein. Negri, S., Oberson, A., Steinmann, M., Sauser, C., Nicod, P., Waeber, G., Schorderet, D.F., Bonny, C. Genomics (2000) [Pubmed]
  12. Activation of the c-Jun N-terminal kinase (JNK) signaling pathway is essential during PBOX-6-induced apoptosis in chronic myelogenous leukemia (CML) cells. Mc Gee, M.M., Campiani, G., Ramunno, A., Nacci, V., Lawler, M., Williams, D.C., Zisterer, D.M. J. Biol. Chem. (2002) [Pubmed]
  13. The fusion protein AML1-ETO in acute myeloid leukemia with translocation t(8;21) induces c-jun protein expression via the proximal AP-1 site of the c-jun promoter in an indirect, JNK-dependent manner. Elsässer, A., Franzen, M., Kohlmann, A., Weisser, M., Schnittger, S., Schoch, C., Reddy, V.A., Burel, S., Zhang, D.E., Ueffing, M., Tenen, D.G., Hiddemann, W., Behre, G. Oncogene (2003) [Pubmed]
  14. Stage IB1 vs IB2 carcinoma of the cervix: should the new FIGO staging system define therapy? Grigsby, P.W. Gynecol. Oncol. (1996) [Pubmed]
  15. Amyloid beta protein precursor (AbetaPP), but not AbetaPP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1. Matsuda, S., Matsuda, Y., D'Adamio, L. J. Biol. Chem. (2003) [Pubmed]
  16. JNK-interacting protein 1 promotes Akt1 activation. Kim, A.H., Sasaki, T., Chao, M.V. J. Biol. Chem. (2003) [Pubmed]
  17. Cross-talk between JIP3 and JIP1 during glucose deprivation: SEK1-JNK2 and Akt1 act as mediators. Song, J.J., Lee, Y.J. J. Biol. Chem. (2005) [Pubmed]
  18. Variations in IB1/JIP1 expression regulate susceptibility of beta-cells to cytokine-induced apoptosis irrespective of C-Jun NH2-terminal kinase signaling. Ling, Z., Van de Casteele, M., Dong, J., Heimberg, H., Haefliger, J.A., Waeber, G., Schuit, F., Pipeleers, D. Diabetes (2003) [Pubmed]
  19. Correlation between the treated volume, the GTV and the CTV at the time of brachytherapy and the histopathologic findings in 33 patients with operable cervix carcinoma. Muschitz, S., Petrow, P., Briot, E., Petit, C., De Crevoisier, R., Duvillard, P., Morice, P., Haie-Meder, C. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. (2004) [Pubmed]
  20. Dissociation of Akt1 from its negative regulator JIP1 is mediated through the ASK1-MEK-JNK signal transduction pathway during metabolic oxidative stress: a negative feedback loop. Song, J.J., Lee, Y.J. J. Cell Biol. (2005) [Pubmed]
  21. Reverse two-hybrid screening identifies residues of JNK required for interaction with the kinase interaction motif of JNK-interacting protein-1. Barr, R.K., Hopkins, R.M., Watt, P.M., Bogoyevitch, M.A. J. Biol. Chem. (2004) [Pubmed]
  22. The JNK interacting protein JIP-1 and insulin like growth factor II genes are co-expressed in human embryonic tumours. Engström, W., Rising, A., Grip, S. Anticancer Res. (2005) [Pubmed]
  23. The JIP group of mitogen-activated protein kinase scaffold proteins. Yasuda, J., Whitmarsh, A.J., Cavanagh, J., Sharma, M., Davis, R.J. Mol. Cell. Biol. (1999) [Pubmed]
  24. Hyperphosphorylation of JNK-interacting protein 1, a protein associated with Alzheimer disease. D'Ambrosio, C., Arena, S., Fulcoli, G., Scheinfeld, M.H., Zhou, D., D'Adamio, L., Scaloni, A. Mol. Cell Proteomics (2006) [Pubmed]
  25. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer. Reesink-Peters, N., van der Velden, J., Ten Hoor, K.A., Boezen, H.M., de Vries, E.G., Schilthuis, M.S., Mourits, M.J., Nijman, H.W., Aalders, J.G., Hollema, H., Pras, E., Duk, J.M., van der Zee, A.G. J. Clin. Oncol. (2005) [Pubmed]
  26. Sentinel node biopsy is reliable in early-stage cervical cancer but not in locally advanced disease. Barranger, E., Coutant, C., Cortez, A., Uzan, S., Darai, E. Ann. Oncol. (2005) [Pubmed]
  27. Operable Stages IB and II cervical carcinomas: a retrospective study comparing preoperative uterovaginal brachytherapy and postoperative radiotherapy. Atlan, D., Touboul, E., Deniaud-Alexandre, E., Lefranc, J.P., Antoine, J.M., Jannet, D., Lhuillier, P., Uzan, M., Huart, J., Genestie, C., Antoine, M., Jamali, M., Ganansia, V., Milliez, J., Uzan, S., Blondon, J. Int. J. Radiat. Oncol. Biol. Phys. (2002) [Pubmed]
  28. A comparison of stages IB1 and IB2 cervical cancers treated with radical hysterectomy. Is size the real difference? Rutledge, T.L., Kamelle, S.A., Tillmanns, T.D., Gould, N.S., Wright, J.D., Cohn, D.E., Herzog, T.J., Rader, J.S., Gold, M.A., Johnson, G.A., Walker, J.L., Mannel, R.S., McMeekin, D.S. Gynecol. Oncol. (2004) [Pubmed]
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