Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prognostic factors in oligodendrogliomas are not well defined, even considering the labeling index of proliferation markers. As in other neuroepithelial tumors, the difficulty in calculating cell loss may contribute to this uncertainty. Proliferation markers Ki-67/MIB.1 and PCNA, mitoses, apoptotic nuclei, p53 and bcl-2 expression were investigated in 98 oligodendrogliomas. Apoptosis was assessed by the aspect of nuclei, by in situ end-labeling (ISEL) technique and by c-Jun immunohistochemical demonstration. The Bcl-2 also was immunohistochemically studied for its anti-apoptotic role. Mitotic index (MI), labeling index (LI) for MIB.1 and PCNA and apoptotic index (AI) were calculated and compared among themselves and with histology and survival. It was found that AI correlated with MI (p = 0.001) and was significantly higher in anaplastic than in classic oligodendrogliomas (p = 0.001). Apoptosis occurred only slightly more frequently in cases with high LIs for proliferation markers (MIB.1 and PCNA) (p = non-significant) and it was definitely higher in p53-positive cases (p = 0.008). It did not correlate with bcl-2 which was poorly expressed in oligodendrogliomas, with the exception of cells with astrocytic features. Apoptotic index correlated very weakly with survival (p = 0.05); therefore, it cannot be considered a highly reliable prognostic factor in oligodendrogliomas.
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PMID:Role of apoptosis in the prognosis of oligodendrogliomas. 922 Apr 57

Solar UV irradiation is the causal factor for the increasing incidence of human skin carcinomas. The activation of the transcription factor activator protein-1 (AP-1) has been shown to be responsible for the tumor promoter action of UV light in mammalian cells. We demonstrate that proteinase inhibitor I (Inh I) and II (Inh II) from potato tubers, when applied to mouse epidermal JB6 cells, block UV-induced AP-1 activation. The inhibition appears to be specific for UV-induced signal transduction for AP-1 activation, because these inhibitors did not block UV-induced p53 activation nor did they exhibit any significant influence on epidermal growth factor-induced AP-1 transactivation. Furthermore, the inhibition of UV-induced AP-1 activity occurs through a pathway that is independent of extracellular signal-regulated kinases and c-Jun N-terminal kinases as well as P38 kinases. Considering the important role of AP-1 in tumor promotion, it is possible that blocking UV-induced AP-1 activity by Inh I or Inh II may be functionally linked to irradiation-induced cell transformation.
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PMID:Proteinase inhibitors I and II from potatoes specifically block UV-induced activator protein-1 activation through a pathway that is independent of extracellular signal-regulated kinases, c-Jun N-terminal kinases, and P38 kinase. 934 44

The ras proto-oncogene is frequently mutated in human tumors and functions to chronically stimulate signal transduction cascades resulting in the synthesis or activation of specific transcription factors, including Ets, c-Myc, c-Jun, and nuclear factor kappa B (NF-kappaB). These Ras-responsive transcription factors are required for transformation, but the mechanisms by which these proteins facilitate oncogenesis have not been fully established. Oncogenic Ras was shown to initiate a p53-independent apoptotic response that was suppressed through the activation of NF-kappaB. These results provide an explanation for the requirement of NF-kappaB for Ras-mediated oncogenesis and provide evidence that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product.
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PMID:Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras. 938 87

Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retinal tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.
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PMID:Death in a dish: controls of apoptosis within the developing retinal tissue. 939 92

p202 is a primarily nuclear, interferon-inducible murine protein that is encoded by the Ifi 202 gene. Overexpression of p202 in transfected cells retards cell proliferation. p202 modulates the pattern of gene expression by inhibiting the activity of various transcription factors including NF-kappaB, c-Fos, c-Jun, E2F-1, and p53. Here we report that p202 was constitutively expressed in mouse skeletal muscle and that the levels of 202 RNA and p202 greatly increased during the differentiation of cultured C2C12 myoblasts to myotubes. When overexpressed in transfected myoblasts, p202 inhibited the expression of one muscle protein (MyoD) without affecting the expression of a second one (myogenin). Thus, the decrease in the level of MyoD (but not of myogenin) during muscle differentiation may be the consequence of the increase in p202 level. Overexpressed p202 also inhibited the transcriptional activity of both MyoD and myogenin. This inhibition was correlated with an interaction of p202 with both proteins, as well as the inhibition by p202 of the sequence-specific binding of both proteins to DNA. This inhibition of the expression of MyoD and of the transcriptional activity of MyoD and myogenin may account for the inhibition of the induction of myoblast differentiation by premature overexpression of p202.
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PMID:Increase in p202 expression during skeletal muscle differentiation: inhibition of MyoD protein expression and activity by p202. 944 5

Jun N-terminal kinase (JNK1) is a member of a family of stress-activated protein kinases which are activated by many forms of stress including UV radiation, resulting in the phosphorylation of c-Jun, ATF-2, Elk-1 and p53. As UV-B radiation is mainly responsible for ultraviolet (UV)-induced skin cancers, we chose to elucidate JNK1 activation in keratinocytes which represent a UV-relevant cell system. We have demonstrated rapid activation of JNK1 in a keratinocyte cell line, C50, in response to multiple doses of UV-B irradiation. JNK1 activation occurred within 1 min, peaked by 10 min and returned to near basal levels within 2 h following the UV-B treatments. Our data provide the first evidence to show that keratinocytes do respond to multiple doses of the physiologically relevant UV-B radiation through rapid activation of the JNK1 pathway.
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PMID:Rapid activation of JNK1 in UV-B irradiated epidermal keratinocytes. 952 48

Simian virus (SV40) T antigen shares many characteristics with adenovirus E1A which is known to induce apoptosis. To verify the potential of SV40 T antigen-mediated apoptosis, we stably expressed T antigen in immortalized human epithelial cells (Z172 and HaCaT). We found that SV40 T antigen could directly cause apoptosis in 22-27% of these cells under normal growth condition as measured by chromatin condensation and nucleosomal fragmentation. The apoptosis of HaCaT cells which contain mutant p53 suggests the p53-independent nature of T antigen-mediated apoptosis. T antigen-induced apoptosis was associated with increased expression of c-Jun protein. Moreover, the overexpression of c-jun alone in these cells also induced apoptosis, indicating that c-jun might play an important role in T antigen-induced apoptosis.
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PMID:The induction of apoptosis by SV40 T antigen correlates with c-jun overexpression. 960 20

Tumor suppressor gene p53 is a critical regulator of the cellular response to DNA damage. To examine the function of p53 in postmitotic CNS neurons, we cultured cerebellar granule cells from 15-day-old wild type and p53-deficient mice, and analyzed changes of protein expression in apoptosis elicited by DNA damage. When cerebellar granule cells from wild type mice were treated with bleomycin, a DNA strand-break inducing agent, neuronal death occurred. In contrast, cells from p53-deficient mice were resistant to bleomycin-induced neuronal death. Furthermore, cells from p53 heterozygous mice showed an intermediate resistance between wild type and p53-deficient mice. These results show that p53 is required for the bleomycin-induced cerebellar granule cell death. To examine which proteins are involved in this apoptosis, we examined changes in protein levels of the Bcl-2 family, including Bcl-2, Bcl-X and Bax. The relative amounts of these proteins did not change after bleomycin treatment, suggesting that the changes in the levels of these Bcl-2 family proteins are not necessary for apoptosis in this system. In contrast, the levels of c-Jun protein significantly increased 6 h after treatment with bleomycin in wild type but not in p53-deficient cerebellar granule cells. These results raise the possibility that c-Jun is required for p53-dependent neuronal apoptosis induced by bleomycin.
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PMID:Changes in c-Jun but not Bcl-2 family proteins in p53-dependent apoptosis of mouse cerebellar granule neurons induced by DNA damaging agent bleomycin. 962 42

p202 is an interferon (IFN)-inducible, primarily nuclear, phosphoprotein (52-kDa) whose overexpression in transfected cells inhibits colony formation. p202 binds to the retinoblastoma tumor suppressor protein and two other members of the pocket family proteins (p107 and p130). Moreover, overexpression of p202 in transfected cells inhibits the transcriptional activity of E2Fs (E2F-1/DP-1 and E2F-4/DP-1), p53, AP-1 c-Fos and c-Jun, NF-kappaB p50 and p65. Here we demonstrate that inhibition of endogenous p202 production in murine AKR-2B fibroblasts did not result in an increase in cell proliferation. Instead, these cells exhibited increased susceptibility to apoptosis in response to decrease in serum concentrations in the growth medium. These observations are consistent with the notion that normal levels of p202 may be needed for the regulation of cell proliferation.
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PMID:p202 prevents apoptosis in murine AKR-2B fibroblasts. 964 35

6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN or CD437), originally identified as a retinoic acid receptor gamma-selective retinoid, was previously shown to induce growth inhibition and apoptosis in human breast cancer cells. In this study, we investigated the role of AHPN/CD437 and its mechanism of action in human lung cancer cell lines. Our results demonstrated that AHPN/CD437 effectively inhibited lung cancer cell growth by inducing G0/G1 arrest and apoptosis, a process that is accompanied by rapid induction of c-Jun, nur77, and p21(WAF1/CIP1). In addition, we found that expression of p53 and Bcl-2 was differentially regulated by AHPN/CD437 in different lung cancer cell lines and may play a role in regulating AHPN/CD437-induced apoptotic process. On constitutive expression of the c-JunAla(63,73) protein, a dominant-negative inhibitor of c-Jun, in A549 cells, nur77 expression and apoptosis induction by AHPN/CD437 were impaired, whereas p21(WAF1/CIP1) induction and G0/G1 arrest were not affected. Furthermore, overexpression of antisense nur77 RNA in A549 and H460 lung cancer cell lines largely inhibited AHPN/CD437-induced apoptosis. Thus, expression of c-Jun and nur77 plays a critical role in AHPN/CD437-induced apoptosis. Together, our results reveal a novel pathway for retinoid-induced apoptosis and suggest that AHPN/CD437 or analogs may have a better therapeutic efficacy against lung cancer.
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PMID:Molecular determinants of AHPN (CD437)-induced growth arrest and apoptosis in human lung cancer cell lines. 967 82


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