The scaffold protein IB1/JIP-1 is a critical mediator of cytokine-induced apoptosis in pancreatic β cells

Haefliger, Jacques‐Antoine; Tawadros, Thomas; Meylan, Laure; Gurun, Sabine Le; Roehrich, Marc-Estienne; Martín, David; Thorens, Bernard; Waeber, Gérard

doi:10.1242/jcs.00356

Cited by 52 publications

(56 citation statements)

References 31 publications

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“…In pancreatic ␤-cells, the scaffold protein termed JNK-interacting protein 1 (JIP-1) or islet-brain 1 (IB1) (41, 60) is required for proper JNK activation and may play a critical role in the pro-apoptotic program observed during diabetes (38,60,61). We demonstrated recently (62) that IB1-JIP-1 content in insulin-producing ␤-cells is critical for ␤-cell function (38) and that an IB1/JIP-1 promoter variant was associated with Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 99%

“…We demonstrated recently (62) that IB1-JIP-1 content in insulin-producing ␤-cells is critical for ␤-cell function (38) and that an IB1/JIP-1 promoter variant was associated with Alzheimer's disease. We have shown recently that the absence of REST allows the cell-specific expression of the human IB1 gene (31).…”

Section: Discussionmentioning

confidence: 99%

“…␤-Cells and neuronal cells share similarities as both cell types are electrically excitable and may respond to hormonal stimuli and glucose by depolarization and exocytosis in a process similar to neurotransmitter release from synaptic vesicles (18,63). Among genes that are linked to a direct pancreatic ␤-cell function, Cx36 (13-17, 38, 41, 60, 61) and IB1/JIP-1 (38,61) are the first found to be regulated by NRSF/REST (31).…”

Section: Discussionmentioning

confidence: 99%

“…Probes were prepared using the following cDNA clones for rat Cx36 (7, 13), for rat IB1/JIP-1 (38,41), and for ␤-actin (42). Hybridizations were performed overnight at 42°C in the presence of 5ϫ SSPE, 50% formamide, 5ϫ Denhardt's solution, 5% SDS, and 100 g/ml purified salmon sperm DNA.…”

Section: Connexin36 Gene Expression Is Controlled By Nrsf/restmentioning

confidence: 99%

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Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines

Martín

Tawadros

Meylan

et al. 2003

Journal of Biological Chemistry

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Adjacent cells share ions, second messengers, small metabolites, and signaling molecules with a weight as high as 1000 Da (1) through intercellular channels that form gap junctions. This type of intercellular communication permits coordinated cellular activity and allows cells to review the functional state of their neighbors, a critical feature for the homeostasis of multicellular organisms (1-4). Intercellular channels result from the association of two half-channels named connexons, which are contributed to separately by each of two adjacent cells. Each connexon is an assembly of membrane proteins named connexins, which are encoded by a gene family consisting of at least 20 members (5, 6).It has been reported that Cx36 1 is the predominantly expressed connexin in rodent neuronal cells (7-9). Immunogold labeling using freeze-fracture replicas have shown that Cx36 was found only in neurons (10) and indicate that the specific expression of connexins by the different cell types of the nervous system may define separate pathways for neuronal versus glial gap junction communication (10 -12). We recently found that Cx36 is the predominant if not the sole connexin isoform expressed in insulin-producing ␤-cells of rat and mouse pancreatic islets (13,14). Recently, Cx36 content was modified in insulin-secreting cells by using an adenoviral gene transfer approach (15) or a lentivirus-mediated transduction of cx36 cDNA (16) in order to evaluate the contribution of Cx36 in the control of insulin secretion and content. These experiments have demonstrated that tight levels of Cx36 are crucial for proper function of insulin-producing cells. Moreover, stably transfected insulin-secreting MIN6 cells with a cx36 antisense cDNA impaired the synchronization of glucose-induced Ca( 2ϩ ) oscillations and insulin secretion in response to glucose (17). These data provided evidence that proper storage of insulin as well as the regulation of insulin release required that the levels of Cx36 be maintained within native values.The objective of the present study was to characterize the mechanisms of cell-specific expression of Cx36. The presence of several gene transcripts in pancreatic ␤-cells and neuronal cells was correlated with the absence in these cell types of a transcription factor named NRSF/REST (neuron-restrictive silencer factor/repressor element silencing transcription factor) (18). NRSF/REST binds to a 21-bp cis element named neuronal restrictive silencer element (NRSE). Through this NRSE, NRSF/REST has been identified as a negative regulatory system that silences neuronal gene expression in non-neuronal tissues, neuronal precursor cells, and certain differentiated

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Connexin36 Gene Expression Is Controlled By Nrsf/restmentioning

confidence: 99%

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Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines

Martín

Tawadros

Meylan

et al. 2003

Journal of Biological Chemistry

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“…Ex vivo, this mutation reduces the stability of IB1 leading to acceleration of the rate of cell apoptosis (23,24). Reduction in IB1 levels with the use of an adenovirus-mediated antisense cDNA leads to a concomitant increase in JNK activity and apoptotic rate (25). In contrast, overexpression of IB1 prevents IL-1␤-mediated activation of JNK and renders the cells more resistant to apoptosis (25).…”

mentioning

confidence: 99%

Exendin-4 Protects β-Cells From Interleukin-1β–Induced Apoptosis by Interfering With the c-Jun NH2-Terminal Kinase Pathway

Ferdaoussi

Abdelli²,

Yang³

et al. 2008

Diabetes

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137

114

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OBJECTIVE— The pro-inflammatory cytokine interleukin-1β (IL-1β) generates pancreatic β-cells apoptosis mainly through activation of the c-Jun NH2-terminal kinase (JNK) pathway. This study was designed to investigate whether the long-acting agonist of the hormone glucagon-like peptide 1 (GLP-1) receptor exendin-4 (ex-4), which mediates protective effects against cytokine-induced β-cell apoptosis, could interfere with the JNK pathway. RESEARCH DESIGN AND METHODS— Isolated human, rat, and mouse islets and the rat insulin-secreting INS-1E cells were incubated with ex-4 in the presence or absence of IL-1β. JNK activity was assessed by solid-phase JNK kinase assay and quantification of c-Jun expression. Cell apoptosis was determined by scoring cells displaying pycnotic nuclei. RESULTS— Ex-4 inhibited induction of the JNK pathway elicited by IL-1β. This effect was mimicked with the use of cAMP-raising agents isobutylmethylxanthine and forskolin and required activation of the protein kinase A. Inhibition of the JNK pathway by ex-4 or IBMX and forskolin was concomitant with a rise in the levels of islet-brain 1 (IB1), a potent blocker of the stress-induced JNK pathway. In fact, ex-4 as well as IBMX and forskolin induced expression of IB1 at the promoter level through cAMP response element binding transcription factor 1. Suppression of IB1 levels with the use of RNA interference strategy impaired the protective effects of ex-4 against apoptosis induced by IL-1β. CONCLUSIONS— The data establish the requirement of IB1 in the protective action of ex-4 against apoptosis elicited by IL-1β and highlight the GLP-1 mimetics as new potent inhibitors of the JNK signaling induced by cytokines.

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Emerging role of the Jun N‐terminal kinase interactome in human health

Guo

Yang

et al. 2018

Cell Biology International

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The c-Jun N-terminal kinases (JNKs) are located downstream of Ras-mitogen activated protein kinase signaling cascades. More than 20 years of study has shown that JNKs control cell fate and many cellular functions. JNKs and their interacting proteins form a complicated network with diverse biological functions and physiological effects. Members of the JNK interactome include Jun, amyloid precursor protein, and insulin receptor substrate. Recent studies have shown that the JNK interactome is involved in tumorigenesis, neuron development, and insulin resistance. In this review, we summarize the features of the JNK interactome and classify its members into three groups: upstream regulators, downstream effectors, and scaffold partners. We also highlight the unique cellular signaling mechanisms of JNKs and provide more insights into the roles of the JNK interactome in human diseases.

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The scaffold protein IB1/JIP-1 is a critical mediator of cytokine-induced apoptosis in pancreatic β cells

Abstract: SummaryThe scaffold protein IB1/JIP-1 is a critical mediator of cytokine-induced apoptosis in pancreatic β cells

Cited by 52 publications

References 31 publications

Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines

Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines

Exendin-4 Protects β-Cells From Interleukin-1β–Induced Apoptosis by Interfering With the c-Jun NH2-Terminal Kinase Pathway

Emerging role of the Jun N‐terminal kinase interactome in human health

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