Islet-Brain1/JNK-interacting Protein-1 Is Required for Early Embryogenesis in Mice

Thompson, Nancy; Haefliger, Jacques‐Antoine; Senn, A.; Tawadros, Thomas; Magara, Fulvio; Ledermann, Birgit; Nicod, Pascal; Waeber, Gérard

doi:10.1074/jbc.c100222200

Cited by 51 publications

(41 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the expression of the IB1 gene has been shown to be mainly detected in neuronal and pancreatic ␤ cells, several reports, including ours, have described low levels of IB1 transcripts in some tissues such as testis and kidney tissues (2,9,22,34), where REST transcripts have been detected (25). One explanation for this observation would be that these cells display a low level of REST expression which is sufficient to decrease IB1 gene expression.…”

Section: Discussionmentioning

confidence: 56%

The Transcriptional Repressor REST Determines the Cell-Specific Expression of the Human MAPK8IP1 Gene Encoding IB1 (JIP-1)

Abderrahmani¹,

Steinmann²,

Plaisance³

et al. 2001

Molecular and Cellular Biology

Self Cite

103

View full text Add to dashboard Cite

Islet-brain 1 (IB1) is the rat and human homologue of JIP-1, a murine inhibitor of the c-Jun amino-terminal kinase (JNK). It was termed IB1 since its expression is mostly detectable in pancreatic islets and in the brain (2). IB1 was identified by studying the transcriptional mechanisms responsible for the pancreatic ␤-cell-specific control of glucose transporter gene GLUT2 (2,4,24,36). Subsequently, the human MAPK8IP1 gene, encoding IB1, was established as a candidate gene for diabetes mellitus (35). Indeed, the direct sequencing of this gene in human type 2 diabetes patients revealed the presence of a missense mutation (resulting in protein mutation S59N) which cosegregated with a rare form of monogenic type 2 diabetes. Ex vivo, this mutation was shown to induce an accelerated apoptosis in pancreatic ␤ cells (35). These observations identified IB1 as a key regulator for ␤-cell survival since it modulates the activation of the JNK signaling pathway, a system which plays an essential role in maturation, differentiation, and/or apoptosis (8, 16). For example, when the IB1 protein content is decreased, ␤ cells are more sensitive to cytokineinduced apoptosis by increasing the JNK activity (3). Thus, the IB1 expression level is critical for ␤-cell function.The goal of the present study was to understand how MAPK8IP1 gene expression is controlled in a tissue-specific manner. Work by Atouf and coauthors has correlated the selective presence of several gene transcripts in pancreatic ␤ and neuronal cells with the absence in these cells of a transcription factor named REST (RE-1 silencing transcription factor, also termed as NRSF) (1). This protein is a zinc finger transcriptional repressor found to be widely expressed during embryogenesis in all tissues, except in endocrine pancreas and mature neuronal tissues (1, 5). The REST gene displays modular organization conserved across humans, rats, and mice within the protein-coding region and is regulated by alternative splicing of REST pre-mRNA. It was reported that the REST isoform with nine zinc fingers is the most predominant isoform found in various tissues (25). Alternatively spliced REST protein isoforms differ in their DNA-binding domains and transrepression domains (26), suggesting different functions of REST. For example, the REST4 isoform, which is a truncated protein, inhibits REST activity by acting as a dominant-negative form of REST (DNREST) (26,32). REST binds to a 21-bp cis element called the RE-1 silencer element (NRSE), also known as repressor element RE-1, to negatively regulate in nonneuronal tissues several genes preferentially expressed in neuronal cells such as the rat SCG10, the rat type II sodium channel, the human synapsin I, and the rat N-methyl-D-aspartate (NMDA) receptor 1 genes (6,18,20,33). The repression effect induced by REST required the interaction of REST with the corepressor mSin3 and histone deacetylase I (HDACI) to form a complex which induces hypoacetylation of histone (15). These authors proposed that a remodeling of the chromatin stru...

show abstract

Section: Discussionmentioning

confidence: 56%

The Transcriptional Repressor REST Determines the Cell-Specific Expression of the Human MAPK8IP1 Gene Encoding IB1 (JIP-1)

Abderrahmani¹,

Steinmann²,

Plaisance³

et al. 2001

Molecular and Cellular Biology

Self Cite

103

View full text Add to dashboard Cite

show abstract

“…To evaluate the potential role of IB1/JIP-1 in the control of JNK activation in islets, we measured the JNK activity in the islets of mice in which the gene encoding IB1/JIP-1 had been disrupted. Because the homozygote IB1/JIP-1 (-/-) mice are associated with embryonic lethality (Tawadros et al, 2002;Thompson et al, 2001), we studied heterozygous IB1/JIP-1 (+/-) mice. These mice have a normal phenotype but the IB1/JIP-1 content is decreased (Fig.…”

Section: Resultsmentioning

confidence: 99%

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

Haefliger¹,

Tawadros²,

Meylan³

et al. 2003

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, JIP1 and JIP3 are structurally distinct proteins (7). Jip1 is not an essential gene, and Jip1 Ϫ/Ϫ mice are viable and fertile with no detected developmental defects (12), although Jip1 gene disruption may cause a preimplantation lethal phenotype in some mouse-strain genetic backgrounds (20). The viable Jip1 Ϫ/Ϫ mice exhibit defects in neuronal apoptosis caused by excitotoxins and ischemia (12).…”

Section: Discussionmentioning

confidence: 99%

Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3)

Kelkar

Delmotte

Weston

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The murine JNK-interacting protein 3 (JIP3) protein (also known as JSAP1) is expressed exclusively in neurons and has been identified as a scaffold protein for the c-Jun NH 2-terminal kinase (JNK) signaling pathway and as an adapter protein for cargo transport by the microtubule motor protein kinesin. To investigate the physiological function of JIP3, we examined the effect of Jip3 gene disruption in mice. The Jip3 ؊/؊ mice were unable to breathe and died shortly after birth. Microscopic analysis demonstrated that Jip3 gene disruption causes severe defects in the morphogenesis of the telencephalon. Jip3 ؊/؊ mice lack the telencephalic commissure, a major connection between the left and right hemispheres of the brain. The central nervous system abnormalities of Jip3 ؊/؊ mice may be accounted for in part by a reduction in signal transduction by RhoA and its effector ROCK.

show abstract

Islet-Brain1/JNK-interacting Protein-1 Is Required for Early Embryogenesis in Mice

Cited by 51 publications

References 27 publications

The Transcriptional Repressor REST Determines the Cell-Specific Expression of the Human MAPK8IP1 Gene Encoding IB1 (JIP-1)

The Transcriptional Repressor REST Determines the Cell-Specific Expression of the Human MAPK8IP1 Gene Encoding IB1 (JIP-1)

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

Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3)

Contact Info

Product

Resources

About