p53-Independent Cyclin G Expression in a Group of Mature Neurons and Its Enhanced Expression during Nerve Regeneration

Morita, Nagayoshi; Kiryu, Sumiko; Kiyama, Hiroshi

doi:10.1523/jneurosci.16-19-05961.1996

Cited by 46 publications

(30 citation statements)

References 24 publications

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“…Taken together, our results indicate that cyclin G1 is involved in G2/M checkpoint control as a downstream mediator of p53 and also plays a role in promotion of cell growth following recovery from damage. In relation to the latter function of cyclin G1, Morita et al reported that nerve injury upregulated the expression of cyclin G1 mRNA in motoneurons during the early phase of the nerve regeneration process, suggesting the involvement of cyclin G1 in the early stages of nerve regeneration (Morita et al, 1996). This expression of cyclin G1 was independent of p53.…”

Section: Discussionmentioning

confidence: 99%

Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

et al. 2001

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Cyclin G1 is one of the target genes of the transcription factor p53, and is induced in a p53-dependent manner in response to DNA damage. Although cyclin G1 has been implicated in a range of biological phenomena, its precise function remains unclear. Here we present an analysis of the physiological role of cyclin G1 using mice homozygous for a targeted disruption of the cyclin G1 gene. In order to clarify the role of cyclin G1 in the p53 pathway, downstream events such as apoptosis, cell growth and cell cycle checkpoint control were analysed in thymocytes and embryonic ®broblasts derived from cyclin G1-disrupted mice. No di erence was detected in induction of apoptosis between mouse embryo ®broblasts (MEFs) derived from cyclin G1 +/+ and cyclin G1 7/7 mice. Following irradiation, cyclin G1 7/7 MEFs proliferated more slowly and reached lower cell densities in culture dishes than cyclin G1 +/+ MEFs. Analysis of cell survival showed that cyclin G1 7/7 MEFs were about twice as sensitive as cyclin G1 +/+ MEFs to g radiation or UV radiation. Cyclin G1 7/7 mice were more sensitive to g radiation than wild-type mice. Flow cytometeric analysis revealed that the number of cyclin G1 7/7 MEFs in G2/ M phase after irradiation was reduced by 50% relative to cyclin G1 +/+ MEFs. Our results demonstrate that cyclin G1 plays roles in G2/M arrest, damage recovery and growth promotion after cellular stress. Oncogene (2001) 20, 3290 ± 3300.

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Section: Discussionmentioning

confidence: 99%

Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

et al. 2001

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“…In an attempt to explore the molecular basis of this process, we have used differential display-PCR to identify genes whose mRNA expression was upregulated in injured hypoglossal motoneurons and succeeded in isolating both novel and known molecules with possible association with neuronal survival and regeneration (Kiryu et al, 1995b;Morita et al, 1996;Su et al, 1997;Namikawa et al, 1998;Toki et al, 1998). In such gene screening studies, molecules restricted to certain intracellular signaling pathways were repeatedly hit.…”

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confidence: 99%

Akt/Protein Kinase B Prevents Injury-Induced Motoneuron Death and Accelerates Axonal Regeneration

Namikawa¹,

Honma

Abe³

et al. 2000

J. Neurosci.

217

169

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Motoneurons require neurotrophic factors for their survival and axonal projection during development, as well as nerve regeneration. By using the axotomy-induced neuronal death paradigm and adenovirus-mediated gene transfer, we attempted to gain insight into the functional significances of major growth factor receptor downstream cascades, Ras-extracellular signalregulated kinase (Ras-ERK) pathway and phosphatidylinositol-3 kinase-Akt (PI3K-Akt) pathway. After neonatal hypoglossal nerve transection, the constitutively active Akt-overexpressing neurons could survive as well as those overexpressing Bcl-2, whereas the constitutively active ERK kinase (MEK)-overexpressing ones failed to survive. A dominant negative Akt experiment demonstrated that inhibition of Akt pathway hastened axotomy-induced neuronal death in the neonate. In addition, the dominant active Akt-overexpressing adult hypoglossal neurons showed accelerated axonal regeneration after axotomy. These results suggest that Akt plays dual roles in motoneuronal survival and nerve regeneration in vivo and that PI3K-Akt pathway is probably more vital in neuronal survival after injury than Ras-ERK pathway.

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“…Among the molecules we have identified as being markedly up-regulated in response to nerve injury (3,4), growth factors, cytokines, and neuropeptides are well established as survival factors for injured neurons (5). These molecules might participate in the protective process as intercellular signaling molecules via secretion in an autocrine or paracrine manner.…”

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confidence: 99%

Damage-induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers

Kiryu‐Seo

Sasaki

Yokohama

et al. 2000

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

109

101

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We isolated a membrane-bound metallopeptidase, DINE (damageinduced neuronal endopeptidase), by differential display PCR using rat normal and axotomized hypoglossal nuclei. The most marked properties of DINE were neuron-specific expression and a striking response to axonal injury in both the central nervous system and peripheral nervous system. For instance, cranial and spinal nerve transection, ischemia, corpus callosum transection, and colchicine treatment increased DINE mRNA expression in the injured neurons, whereas kainate-induced hyperexcitation, immobilization, and osmotic stress failed to up-regulate DINE mRNA. Expression of DINE in COS cells partially inhibited C2-ceramide-induced apoptosis, probably because of the activation of antioxidant enzymes such as Cu͞Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase through the proteolytic activity of DINE. These data provide insight into the mechanism of how injured neurons protect themselves against neuronal death. P eripheral nerve regeneration entails sequential changes in the expression of thousands of genes, which are necessary to protect damaged neurons from death, activate surrounding glial cells, and accelerate neurite elongation. For the last few years, we have attempted to identify molecules involved in this process by using a technique known as differential display PCR (DD-PCR) and random cloning with a specific cDNA library derived from nerve-injured hypoglossal nuclei (1, 2).Among the molecules we have identified as being markedly up-regulated in response to nerve injury (3, 4), growth factors, cytokines, and neuropeptides are well established as survival factors for injured neurons (5). These molecules might participate in the protective process as intercellular signaling molecules via secretion in an autocrine or paracrine manner. Generally, secreted proteins such as neuropeptides and growth factors are biosynthesized as large precursor proteins, and processing occurs in the trans-Golgi network by endoproteolytic serine proteases, which are members of the proprotein convertase (PC) family (6). An increasing number of other secreted proteins now are recognized as being derived from integral plasma membrane proteins by hydrolysis (shedding) on the cell surface (7). Proteins secreted in this fashion include some membrane receptors, receptor ligands, ectoenzymes, and cell adhesion molecules. These ectodomain shedding events have been shown to be associated with metalloprotease inhibitors (8). Since identification of the ADAM (a disintegrin and metalloproteinase) family (9) and MMP (matrix metalloprotease) family, our understanding of the shedding events on the cell surface has greatly improved in recent years.As for nerve regeneration, the repertoire of proteases involved in the process is limited. Among regeneration processes, the roles of proteases in a process of axon elongation are relatively well studied both in vitro and in vivo. It has been assumed that this axonal behavior is, for instance, a consequence of the bala...

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p53-Independent Cyclin G Expression in a Group of Mature Neurons and Its Enhanced Expression during Nerve Regeneration

Cited by 46 publications

References 24 publications

Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

Akt/Protein Kinase B Prevents Injury-Induced Motoneuron Death and Accelerates Axonal Regeneration

Damage-induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers

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