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

• We therefore hypothesized that IB1/JIP-1 is a risk factor for Alzheimer's disease (AD) [6].

High impact information on Mapk8ip1

• In addition, JIP-1 suppressed the effects of the JNK signaling pathway on cellular proliferation, including transformation by the Bcr-Abl oncogene [7].
• An essential role of the JIP1 scaffold protein for JNK activation in adipose tissue [2].
• JIP1 is located in the neurites of primary hippocampal neurons [8].
• These data show that the JIP1 scaffold protein is a critical component of a MAP-kinase signal transduction pathway [8].
• Down-regulation of JIP-1 by small interfering RNA specifically impairs transport of pAPP, with no effect on the trafficking of nonphosphorylated APP [9].

Biological context of Mapk8ip1

• JIP1 mediated the activation of JNK1 induced by glucose deprivation in mouse embryonic fibroblasts, and ectopic expression of Notch1-IC inhibited JNK activation and apoptosis triggered by glucose deprivation [10].
• Taken together, these results suggest that increased alpha-synuclein expression might protect cells from oxidative stress by inactivation of JNK via increased expression of JIP-1b/IB1 [11].
• Islet-brain1/JNK-interacting protein-1 is required for early embryogenesis in mice [12].
• In culture, no IB1/JIP-1(-/-) embryos were identified indicating that accelerated cell death occurred during the first cell cycles [12].
• Using a viral gene transfer approach, the stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1 [13].

Anatomical context of Mapk8ip1

• The transgenic JIP1 partially rescued the axon guidance defect of the corpus callosum and the anterior commissure of the jsap1-/- brain [14].
• Taken together, these data indicate that IB1/JIP-1 in hippocampus participates in the regulation of the neuronal response to excitotoxic stress in a level-dependent fashion [1].
• IB1 was located in axonal and dendritic growth cones in primary telencephalon cells [15].
• IB1 was also detected in a restricted number of axons, as in the mossy fibres from dentate gyrus in the hippocampus, and was found in soma, dendrites and axons of cerebellar Purkinje cells [15].
• IB1/JIP-1 expression was detected in unfertilized oocytes, in spermatozoa, and in different stages of embryo development [12].

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

• Requirement of the JIP1 scaffold protein for stress-induced JNK activation [8].
• Krox-20 also up-regulates the scaffold protein JNK-interacting protein 1 (JIP-1) [19].

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

• Here, IB1 was studied in adult and developing mouse brain tissue by in situ hybridization, Northern and Western blot analysis at cellular and subcellular levels, as well as by immunocytochemistry in brain sections and cell cultures [15].
• By mobility shift assay, we confirmed that REST binds to the NRSE present in the IB1 promoter [18].
• Indirect immunofluorescence analysis localized endogenous JIP-1 to the tip of the neurites in differentiated NIE-115 and PC12 cells [22].
• By immunocytochemistry, we first colocalized the presence of IB1/JIP-1 with JNK and phosphorylated tau in neurofibrillary tangles [6].

References