Transcriptional Regulation of 5-Aminolevulinate Synthase by Phenobarbital and cAMP-Dependent Protein Kinase

Varone, Cecilia; Giono, Luciana E.; Ochoa, Alberto; Zakin, Mario M.; Cánepa, Eduardo T.

doi:10.1006/abbi.1999.1470

Cited by 33 publications

(30 citation statements)

References 38 publications

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“…After 18 h, cells were exposed to the genotoxic agents and harvested 24 h later. CAT activity was determined as previously described 62 and normalized to bgalactosidase activity.…”

Section: Chloramphenicol Acetyltransferase Assaymentioning

confidence: 99%

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

et al. 2015

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Abbreviations: ODN, oligodeoxynucleotide; NCS, neocarzinostatin; ASCAT, CAT antisense; ASE2F1, E2F1 antisense; ASE2F2, E2F2 antisense; wt E2F DO, wild-type E2F decoy oligodeoxynucleotide; mut E2F DO, mutant E2F decoy oligodeoxynucleotide.E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with gH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

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“…After 18 h, cells were exposed to the genotoxic agents and harvested 24 h later. CAT activity was determined as previously described 62 and normalized to bgalactosidase activity.…”

Section: Chloramphenicol Acetyltransferase Assaymentioning

confidence: 99%

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

et al. 2015

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“…The ODN and cDNA was purified and 5 0 -end labeled using [c-32 P] ATP and T 4 polynucleotide kinase. Hybridization was carried out overnight at 688C in the same prehybridization solution by adding the 32 P-labeled oligodeoxynucleotide (3 3 10 5 cpm/cm 2 ) as previously described (20). Membranes were stripped, prehybridized, hybridized, and washed in standard conditions as described before (18).…”

Section: Rna Isolation and Northern Blot Analysismentioning

confidence: 99%

E2F1 transcription is induced by genotoxic stress through ATM/ATR activation

et al. 2009

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SummaryE2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

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“…The resulting probe had a specific activity of about 4-6 Â 10 3 cpm/ fmol. Hybridization was carried out overnight at 681C in the same prehybridization solution by adding the 32 P-labeled oligodeoxynucleotide (4 Â 10 5 cpm/cm 2 ) as previously described (Varone et al, 1999). To detect b-tubulin and other mRNAs, the corresponding cDNA was labeled by random priming using [a-32 P]CTP and Klenow to a specific activity of about 5 Â 10 8 cpm/mg.…”

Section: Rna Isolation and Northern Blot Analysismentioning

confidence: 99%

Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells

et al. 2005

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The genetic instability driving tumorigenesis is fuelled by DNA damage and by errors made by the DNA replication. Upon DNA damage the cell organizes an integrated response not only by the classical DNA repair mechanisms but also involving mechanisms of replication, transcription, chromatin structure dynamics, cell cycle progression, and apoptosis. In the present study, we investigated the role of p19INK4d in the response driven by neuroblastoma cells against DNA injury caused by UV irradiation. We show that p19INK4d is the only INK4 protein whose expression is induced by UV light in neuroblastoma cells. Furthermore, p19INK4d translocation from cytoplasm to nucleus is observed after UV irradiation. Ectopic expression of p19INK4d clearly reduces the UV-induced apoptosis as well as enhances the cellular ability to repair the damaged DNA. It is clearly shown that DNA repair is the main target of p19INK4d effect and that diminished apoptosis is a downstream event. Importantly, experiments performed with CDK4 mutants suggest that these p19INK4d effects would be independent of its role as a cell cycle checkpoint gene. The results presented herein uncover a new role of p19INK4d as regulator of DNAdamage-induced apoptosis and suggest that it protects cells from undergoing apoptosis by allowing a more efficient DNA repair. We propose that, in addition to its role as cell cycle inhibitor, p19INK4d is involved in maintenance of DNA integrity and, therefore, would contribute to cancer prevention.

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Transcriptional Regulation of 5-Aminolevulinate Synthase by Phenobarbital and cAMP-Dependent Protein Kinase

Cited by 33 publications

References 38 publications

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

E2F1 transcription is induced by genotoxic stress through ATM/ATR activation

Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells

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