Is c-Jun involved in nerve cell death following status epilepticus and hypoxic-ischaemic brain injury?

Dragunow, Michael; Young, Deborah; Hughes, Paul E.; MacGibbon, Geraldine; Lawlor, P.; Singleton, K.; Sirimanne, Ernest; Beilharz, Erica; Gluckman, Peter D.

doi:10.1016/0169-328x(93)90101-t

Cited by 213 publications

(80 citation statements)

References 35 publications

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“…Overexpression of c-Jun in sympathetic neurons induces apoptosis while a dominant-negative mutant of c-Jun blocks Nerve Growth Factor (NGF) withdrawal-induced programmed cell death (Estus et al, 1994;Ham et al, 1995). Moreover, c-Jun accumulates in neurons undergoing apoptosis by hypoxia in vivo (Dragunow et al, 1993). Amino-terminal phosphorylation of c-Jun is also required for ceramide-induced apoptosis of myeloid or lymphoid tumour cell lines (Verheij et al, 1996) and neuronal stress-induced apoptosis in vivo (Behrens et al, 1999).…”

Section: Apoptosis and Senescencementioning

confidence: 99%

The mammalian Jun proteins: redundancy and specificity

2001

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The AP-1 transcription factor is composed of a mixture of homo-and hetero-dimers formed between Jun and Fos proteins. The di erent Jun and Fos family members vary signi®cantly in their relative abundance and their interactions with additional proteins generating a complex network of transcriptional regulators. Thus, the functional activity of AP-1 in any given cell depends on the relative amount of speci®c Jun/Fos proteins which are expressed, as well as other potential interacting proteins. This diversity of AP-1 components has complicated our understanding of AP-1 function and resulted in a paucity of information about the precise role of individual AP-1 members in distinct cellular processes. We shall discuss recent studies which suggest that di erent Jun and Fos family members may have both opposite and overlapping functions in cellular proliferation and cell fate. Oncogene (2001) 20, 2378 ± 2389.

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Section: Apoptosis and Senescencementioning

confidence: 99%

The mammalian Jun proteins: redundancy and specificity

2001

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“…c-jun is induced in rive in neurons after ischemia (Dragunow et al, 1993); at least a portion of the accompanying neuronal death appears apoptotic because the characteristic nucleosomal ladder is detected (MacManus et al, 1993(MacManus et al, , 1994Linnik et al, 1993) and the size of the infarcted area is reduced by cycloheximide treatment (Linnik et al, 1993). While c-fos knockouts manifest some pathology (Wang et al, 1992;Johnson et al, 1992) that may be reflective of abnormal PCD (Smeyne et al, 1993), our observation that the very similar c-fos andfos B genes were induced in parallel suggests a degree of redundancy and that both may need to be blocked to inhibit neuronal PCD fully, c-jun knockout mice die at ,x, ll.5 d of gestation; it has not been reported whether PCD is abnormal in these mice (Hilberg, 1993;.…”

Section: Role Of Altered Gene Expression In Apoptosismentioning

confidence: 99%

Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis.

Estus

Zaks

Freeman

et al. 1994

The Journal of Cell Biology

794

531

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Abstract. We have examined the hypothesis that neuronal programmed cell death requires a genetic program; we used a model wherein rat sympathetic neurons maintained in vitro are deprived of NGF and subsequently undergo apoptosis. To evaluate gene expression potentially necessary for this process, we used a PCR-based technique and in situ hybridization; patterns of general gene repression and selective gene induction were identified in NGF-deprived neurons. A temporal cascade of induced genes included "immediate early genes;' which were remarkable in that their induction occurred hours after the initial stimulus of NGF removal and the synthesis of some required ongoing protein synthesis. The cascade also included the cell cycle gene c-myb and the genes encoding the extracellular matrix proteases transin and collagenase. Concurrent in situ hybridization and nuclear staining revealed that while c-jun was induced in most neurons, c-fos induction was restricted to neurons undergoing chromatin condensation, a hallmark of apoptosis. To evaluate the functional role of the proteins encoded by these genes, neutralizing antibodies were injected into neurons. Antibodies specific for either c-Jun or the Fos family (c-Fos, Fos B, Fra-1, and Fra-2) protected NGF-deprived neurons from apoptosis, whereas antibodies specific for Jun B, Jun D, or three nonimmune antibody preparations had no protective effect. Because these induced genes encode proteins ranging from a transcription factor necessary for death to proteases likely involved in tissue remodeling concurrent with death, these data may outline a genetic program responsible for neuronal programmed cell death.

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“…Whereas the mechanisms regulating cell death or inhibition of neurite regeneration after axotomy remain unclear, increasing evidence suggests that these are regulated processes, controlled by multiple, discrete biochemical signals (1)(2)(3). Of the signaling pathways associated with neuronal death, a role for the stress-activated protein kinase͞c-Jun N-terminal kinase (SAPK͞JNK) signaling pathway has been implicated in nerve injury (4,5). In this regard, correlative studies have described increased expression of c-Jun and JNK activity after axotomy (6)(7)(8).…”

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confidence: 99%