c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis

Schroeter, Hagen; Boyd, Clinton S; Ahmed, Ruhi; Spencer, Jeremy P.E.; Duncan, Roger; Rice‐Evans, Catherine; Cadenas, Enrique

doi:10.1042/bj20030201

Cited by 155 publications

(123 citation statements)

References 49 publications

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“…The JNK1/2 pathway has been implicated in signalling events in many forms of neuronal apoptosis [36]. In response to a variety of extracellular stimuli, JNK1/2 phosphorylates and regulates the activity of members of the Bcl-2 family (Bcl-2, Bcl-xL, Bim and Bad) [37,38] and modulates Bcl-2 and Bax protein expression [37,39,40].…”

Section: Discussionmentioning

confidence: 99%

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

Muscella

Calabriso

Vetrugno

et al. 2011

Biochemical Pharmacology

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Section: Discussionmentioning

confidence: 99%

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

Muscella

Calabriso

Vetrugno

et al. 2011

Biochemical Pharmacology

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“…However, we cannot rule out the involvement of other adapter proteins, such as HSP, able to transport kinases/phosphatases to mitochondria (53). Recently, the role of JNK and p38 MAPK on mitochondria has been defined in more detail and, besides Bcl-2/Bcl-X L phosphorylation, activation of other pro-apoptotic members of Bcl-2 family (Bim, Bmp) has been reported previously (54) as well as phosphorylation of other ill-defined mitochondrial proteins (55).…”

Section: Ngf Induces Mitochondrial Localization Of Mkp-1 Protein-mentioning

confidence: 99%

Nerve Growth Factor-dependent Survival of CESS B Cell Line Is Mediated by Increased Expression and Decreased Degradation of MAPK Phosphatase 1

Rosini

Chiara

Bonini

et al. 2004

Journal of Biological Chemistry

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The sIgG ؉ lymphoblastoid B cell line CESS spontaneously produces a high amount of nerve growth factor (NGF) and expresses both high affinity (p140 Trk-A ) and low affinity (p75 NTR ) NGF receptors. Autocrine production of NGF maintains the survival of CESS cells through the continuous deactivation of p38 MAPK, an enzyme able to induce Bcl-2 phosphorylation and subsequent cytochrome c release and caspase activation. In this paper, we show that NGF induces transcriptional activation and synthesis of MAPK phosphatase 1 (MKP-1), a dual specificity phosphatase that dephosphorylates p38 MAPK, thus preventing Bcl-2 phosphorylation. Furthermore, NGF increases MKP-1 protein stability by preventing its degradation through the proteasome pathway. Following NGF stimulation, MKP-1 protein mainly localizes on mitochondria, suggesting an interaction with p38 MAPK in this compartment. Incubation of CESS cells with MKP-1-specific antisense oligonucleotides induces cell death, which was not prevented by exogenous NGF. By contrast, overexpression of native MKP-1, but not of its catalytically impaired form, inhibits apoptosis induced by NGF neutralization in CESS cells. Thus, the molecular mechanisms underlying the survival function of NGF in CESS B cell line predominantly consist in maintaining elevated levels of MKP-1 protein, which controls p38 MAPK activation.

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“…suppression of Bcl-2-binding protein BNIP3 expression (41), caspase inhibition by S-nitrosylation (17,18), interruption of the mitochondrial pathway (42)(43)(44)(45) or induction of heat shock proteins (46). It is likely that some of these mechanisms are downstream consequences of NO-mediated CD95-Tyr nitration, which blocks CD95 activation and the activation of upstream caspases, which are required for mitochondrial amplification of the apoptotic signal.…”

Section: Cd95-tyr Nitration and Inhibition Of Apoptosis-inductionmentioning

confidence: 99%

CD95-tyrosine Nitration Inhibits Hyperosmotic and CD95 Ligand-induced CD95 Activation in Rat Hepatocytes

Reinehr

Görg

Höngen

et al. 2004

Journal of Biological Chemistry

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Epidermal growth factor receptor-dependent CD95-tyrosine phosphorylation was recently identified as an early step in apoptosis induction via the CD95 system (Reinehr, R., Schliess, F., and Hä ussinger, D. (2003) FASEB J. 17, 731-733). The effect of peroxynitrite (ONOO ؊ ) on modulation of the hyperosmotic and CD95 ligand (CD95L)-induced CD95 activation process was studied. Pretreatment of hepatocytes with ONOO ؊ inhibited CD95L-and hyperosmolarity-induced CD95 membrane trafficking and formation of the death-inducing signaling complex, but not epidermal growth factor receptor activation and its association with CD95. Under these conditions, however, no tyrosine phosphorylation of CD95 occurred; instead, CD95 was tyrosine-nitrated. When ONOO ؊ was added after induction of CD95-tyrosine phosphorylation by CD95L or hyperosmolarity, tyrosine nitration of CD95 was largely prevented and death-inducing signaling complex formation occurred. CD95-tyrosine nitration abolished the hyperosmotic sensitization of hepatocytes toward CD95L-induced apoptosis. Additionally, in CD95-yellow fluorescent protein-transfected Huh7-hepatoma cells, ONOO ؊ induced CD95 Tyr nitration and prevented CD95L-induced Tyr phosphorylation and apoptosis. Tyrosine-nitrated CD95 was also found in rat livers derived from an in vivo model of endotoxinemia. The data suggest that CD95-tyrosine nitration prevents CD95 activation by inhibiting CD95-tyrosine phosphorylation. Apparently, CD95-tyrosine phosphorylation and nitration are mutually exclusive. The data identify critical tyrosine residues of CD95 as another target of the anti-apoptotic action of NO.Apoptosis plays an important role in the pathogenesis of liver injury with activation of the CD95 1 (also known as Fas/ APO-1) system in response to hyperosmolarity, CD95 ligand, hydrophobic bile acids, or ethanol (1-11). In hepatocytes, CD95 activation is a complex process, which involves rapid activation of the EGFR, its JNK-dependent association with CD95 and subsequent tyrosine phosphorylation of CD95 by the EGFRtyrosine kinase activity (4, 6). CD95-tyrosine phosphorylation then triggers CD95 membrane trafficking, DISC formation and in the case of hydrophobic bile acids and CD95 ligand (CD95L) execution of apoptosis (4, 6). CD95 activation and DISC formation are also triggered by hyperosmotic cell shrinkage; however, despite this hepatocytes do not undergo spontaneous apoptosis, but are sensitized toward CD95L-induced apoptosis (1). The critical role of CD95-tyrosine phosphorylation for apoptosis induction/sensitization is underlined by the findings that inhibitors of EGFR activation or its tyrosine kinase activity abolish CD95 activation, membrane trafficking, and apoptosis (4, 6).Recent studies indicate that nitric oxide (NO) can protect various cell types from apoptotic cell death (12)(13)(14)(15). This protective role of NO involves cyclic guanine monophosphate formation (13), caspase 8 S-nitrosylation, prevention of loss of mitochondrial membrane potential, Bid cleavage, and cytochrome c release ...

show abstract

c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis

Cited by 155 publications

References 49 publications

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

Nerve Growth Factor-dependent Survival of CESS B Cell Line Is Mediated by Increased Expression and Decreased Degradation of MAPK Phosphatase 1

CD95-tyrosine Nitration Inhibits Hyperosmotic and CD95 Ligand-induced CD95 Activation in Rat Hepatocytes

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