Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination

Yan, Chunhong; Lü, Dan; Hai, Tsonwin; Boyd, Douglas D.

doi:10.1038/sj.emboj.7600712

Cited by 187 publications

(273 citation statements)

References 43 publications

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“…These results suggest that HA and NMH induced the same oxidative stress and SIPS via similar (Kang et al 2000), induction of apoptosis (Chung et al 2003) Increase Apoptosis BCL2-associated X protein BAX Pro-apoptotic proteins (Adams and Cory 1998), mitochondrial dysfunction (Gross et al 1998 Activating transcription factor 3 ATF3 Maintaining DNA integrity and protecting against cell transformation (Yan et al 2005) Increase oxygen toxicities, because both conditions have the same oxygen partial pressure. Moreover, the expressions of proteins involved in heat shock and cell cycle check points were not significantly different between the two hyperoxic conditions.…”

Section: Discussionmentioning

confidence: 87%

Comparison of the effects of 40% oxygen and two atmospheric absolute air pressure conditions on stress-induced premature senescence of normal human diploid fibroblasts

Oh¹,

Lee²,

Lee³

et al. 2008

Cell Stress and Chaperones

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The pressure during hyperbaric oxygen treatment may increase oxygen toxicity via an augmented oxygen pressure in the gas. Nevertheless, only a few reports have been published on the effect of cells grown under 2 atmospheric absolute (ATA) pressure. To evaluate the effect of pressure on oxygen toxicity and to study effects in addition to oxygen toxicity, we designed an experiment to compare the effects of normobaric mild hyperoxia (NMH, 40% oxygen) and hyperbaric air condition (HA, air with 2 ATA) on human diploid fibroblasts (HDF) in a hyperbaric incubator. HDFs in both the NMH and the HA condition had a similar oxidative stress response and exhibited premature senescence. To investigate differences in gene profiling in cells grown in the NMH and HA conditions, samples from cells exposed to each condition were applied to microarrays. We found no expression difference in genes related to aging and deoxyribonucleic acid damage, but the expression of genes including cell adhesion, stress response, and transcription were significantly increased in fibroblasts that were responsive to pressure. Among 26 statistically reliable genes, the expression of apoptosis related genes such as ADAM22, Bax, BCL2L14, and UBD, as well as tumor suppressor-related genes like Axin2 and ATF, and also mitogen-activated protein kinase-related genes like mitogen-activated protein kinase kinase kinase 1, histamine receptor, and RAB24, were significantly changed in cells responsive to pressureinduced oxidative stress.

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Section: Discussionmentioning

confidence: 87%

Comparison of the effects of 40% oxygen and two atmospheric absolute air pressure conditions on stress-induced premature senescence of normal human diploid fibroblasts

Oh¹,

Lee²,

Lee³

et al. 2008

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…These genes may also be target genes of HIF-1, since all genes encoding glycolytic enzymes as well as many other metabolic genes were upregulated by hypoxia in a HIF-1-dependent manner. 33 Atf3, which stabilizes p53 tumor suppressor, 34 was upregulated by gold-1a. In addition, the expression of Mmp13 was reported to be dysregulated during cancer progression associated with p53 inactivation, 35 but this gene was down- regulated in response to gold-1a.…”

Section: Discussionmentioning

confidence: 99%

Gold(III) compound is a novel chemocytotoxic agent for hepatocellular carcinoma

Lum

Yang

et al. 2005

Int. J. Cancer

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Recently, a series of gold(III) meso-tetraarylporphyrins that are stable against demetallation in physiological conditions have been synthesized. In the present study, the antitumor effects of one of these compounds, gold(III) meso-tetraarylporphyrin 1a (gold-1a) was investigated in an orthotopic rat hepatocellular carcinoma (HCC) model as well as using a HCC cell line. The rat HCC model was induced by injection of rat hepatoma cells, McA-RH7777, into the left lobe of the liver. Seven days after tumor cell inoculation, gold-1a was injected directly into the tumor nodule at different doses, followed by the same doses via intraperitoneal injection twice a week. Gold-1a administration significantly prolonged the survival of HCC-bearing rats. Importantly, gold-1a induced necrosis as well as apoptosis in the tumor tissues, but not in the normal liver tissues. Furthermore, gold-1a treatment neither caused significant drop in body weight of the rats nor affected plasma aspartate aminotransferase level. In the in vitro studies, we observed that gold-1a treatment inhibited the proliferation of McA-RH7777 cells. Gold-1a upregulated genes that increase apoptosis, stabilize p53, decrease proliferation and downregulated genes playing roles in angiogenesis, invasion, and metabolism, as demonstrated by microarray. In particular, the compound upregulated 2 members of the growth arrest and DNA damage (Gadd) inducible gene family, Gadd34 and Gadd153. Suppression of Gadd34 and Gadd153 in McA-RH7777 cells by small hairpin RNA reduced the gold-1a-induced apoptosis and growth inhibition, indicating that gold-1a mediated its effects via upregulation of Gadd34 and Gadd153. Results from our study demonstrated that gold-1a might be a novel promising chemocytotoxic agent for treating HCC. ' 2005 Wiley-Liss, Inc.Key words: gold(III) compound; chemocytotoxic; hepatocellular carcinoma; apoptosis; growth arrest and DNA damage (Gadd) inducible genes Hepatocellular carcinoma (HCC) ranks fifth in frequency worldwide among all malignancies and causes 1 million deaths annually. 1,2 Over 500,000 new cases are currently diagnosed every year. 3 Hepatic resection and liver transplantation are the only 2 approaches that may cure HCC, but the majority of patients present with an advanced stage beyond surgical treatment. Chemotherapy is widely employed to treat unresectable HCC, 4,5 but the efficacy is not satisfactory because of the resistance of tumor cells to the chemocytotoxic agents.The inorganic complex cis-diamminedichloroplatinum(II) (cisplatin), which possesses potent antitumor activity, 6 has been extensively used to treat various human solid carcinomas. 7 Although cisplatin was effective in treating metastatic nasopharyngeal carcinoma 8,9 and prolonged survival in advanced and metastatic non-small cell lung cancer, 10 its overall response rates in HCC patients were low, and thus it failed to prolong patient survival. 11 Therefore, novel and nontoxic therapeutic agents are urgently needed to treat HCC.Gold compounds have long been shown to pose...

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“…ATF3 has been suggested to be critical in metastasis, and has also been reported to be proapoptotic as well as antiapoptotic (Ishiguro and Nagawa, 2000;Hai and Hartman, 2001;Francis et al, 2004;Hartman et al, 2004). As this paper was Anoxic induction of ATF3 K Ameri et al completed, it was reported that ATF3 stabilizes p53 upon genotoxic stress (Yan et al, 2005), and also induces tubulogenic differentiation in endothelial cells and angiogenesis in diabetic angiopathy (Okamoto et al, 2006). Thus, a potential role of ATF3 in modulating p53 and angiogenesis under anoxia should be investigated.…”

mentioning

confidence: 86%

Induction of activating transcription factor 3 by anoxia is independent of p53 and the hypoxic HIF signalling pathway

et al. 2006

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Solid tumors often have an inadequate blood supply, which results in large regions that are subjected to hypoxic or anoxic stress. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates much of the transcriptional response of cells to hypoxia. Activating transcription factor 3 (ATF3) is another transcription factor that responds to a variety of stresses and is often upregulated in cancer. We investigated the regulation of ATF3 by oxygen deprivation. ATF3 induction occurred most robustly under anoxia, is common, and it is not dependent on presence of HIF-1 or p53, but is sensitive to the inhibition of c-Jun NH2-terminal kinase activation and the antioxidant N-acetylcystein. ATF3 could also be induced by desferrioxamine but not by the mitochondrial poison cyanide or the nonspecific 2-oxoglutarate dioxygenase inhibitor dimethyloxalylglycine. We also show that anoxic ATF3 mRNA is more stable than normoxic mRNA providing a mechanism for this induction. Thus, this study demonstrates that the regulation of ATF3 under anoxia is independent of 2-oxoglutarate dioxygenase, HIF-1 and p53, presumably involving multiple regulatory pathways.

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Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination

Cited by 187 publications

References 43 publications

Comparison of the effects of 40% oxygen and two atmospheric absolute air pressure conditions on stress-induced premature senescence of normal human diploid fibroblasts

Comparison of the effects of 40% oxygen and two atmospheric absolute air pressure conditions on stress-induced premature senescence of normal human diploid fibroblasts

Gold(III) compound is a novel chemocytotoxic agent for hepatocellular carcinoma

Induction of activating transcription factor 3 by anoxia is independent of p53 and the hypoxic HIF signalling pathway

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