Identification of redox/repair protein Ref-1 as a potent activator of p53.

Jayaraman, Lata; Murthy, Kanneganti G.K.; Zhu, Chunhong; Curran, Tom; Xanthoudakis, Steven; Prives, Carol

doi:10.1101/gad.11.5.558

Cited by 441 publications

(319 citation statements)

References 36 publications

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“…It is also likely that CAT affects the cellular redox status, leading to a modulation of gene expression through the activity of various transcription factors such as nuclear factor-kB, Fos, Jun, Myb 48 and p53. 49 Consistent with this hypothesis, it has been reported that UVB-induced ROS are involved in transcriptional activation of AP-1, 50 increased production of matrix metalloproteases 51 and also biosynthesis and activation of transforming growth factor-b. 52 We demonstrated that UVA-induced hypertrophy was decreased by the overexpression of CAT (but not by the overexpression of CuZnSOD or MnSOD).…”

Section: Discussionmentioning

confidence: 63%

Protection of normal human reconstructed epidermis from UV by catalase overexpression

et al. 2006

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Reactive oxygen species (ROS) generated by ultraviolet (UV) irradiation are counterbalanced by endogenous antioxidant systems. To test the hypothesis of a novel photoprotective approach, we irradiated epidermis reconstructed with normal human keratinocytes overexpressing sustainably lentivirus-mediated catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD) or manganese superoxide dismutase (MnSOD) enzymes. We found that following UVB irradiation there was a marked decrease in sunburn cell formation, caspase-3 activation and p53 accumulation in human reconstructed epidermis overexpressing CAT. Moreover, UVA-induced hypertrophy and DNA oxidation (8-oxodeoxyguanosine) were decreased by CAT overexpression. These effects were not achieved by overexpression of CuZnSOD or MnSOD. In conclusion, vector-mediated CAT overexpression could be a promising photoprotective tool against deleterious effects of UV irradiation such skin cancer especially in monogenic/polygenic photosensitive disorders characterized by ROS accumulation.

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Section: Discussionmentioning

confidence: 63%

Protection of normal human reconstructed epidermis from UV by catalase overexpression

et al. 2006

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“…This activity was shown to be activated by various pathways: phosphorylation (Hupp et al, 1992), antibody speci®c for the carboxyterminus of the protein (Hupp et al, 1992), small peptides which could mimic the carboxy-terminus of the p53 (Hupp et al, 1995), short single stranded DNA (Jayaraman and Prives, 1995), deletion of the last 30 amino-acids (Hupp et al, 1992) and the interaction with a cellular protein (Jayaraman et al, 1997). In the present study, we demonstrate that this feature is not unique to Hp53, but can also be extended to Xp53.…”

Section: Discussionmentioning

confidence: 99%

“…The non speci®c binding of small oligonucleotides by the carboxy-terminal region of p53 has also been shown to activate the speci®c DNA binding activity of the central region of p53 (Jayaraman and Prives, 1995). Recently, a cellular protein, ref1, has been shown to be able to convert latent p53 to one that is active for DNA binding (Jayaraman et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Regulation of the specific DNA binding activity of Xenopus laevis p53: evidence for conserved regulation through the carboxy-terminus of the protein

et al. 1998

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Recombinant human p53 isolated either from E. coli or from insect cells is poorly active for binding to DNA but it can be dramatically stimulated by phosphorylation, antibody binding to the carboxy-terminal negative regulatory domain, short peptides derived from this negative regulatory domain or short single strands of DNA. We report here that Xenopus p53 has a very similar behavior. Using a new set of monoclonal antibodies directed either to the amino-or the carboxyterminus of Xenopus p53, we demonstrate that the frog protein can be activated by speci®c carboxy-terminus monoclonal antibodies in order to bind to human p53 DNA response element. In addition, we report that such activation of both humans and frogs protein can also be achieved by small peptides derived from the carboxyterminus of both p53. Although, the sequence of this region is not conserved in the various p53 species, the presence of conserved basic residues indicates that such activation is charge-dependent. This is con®rmed by the ®nding that small poly-lysine peptides can activate both human and Xenopus p53. In vivo expression of Xenopus p53 indicates that this protein is able to transactivate a wide variety of human p53 response elements as long as the experiments are performed at 328C since activity at 378C, a temperature well above the natural temperature of Xenopus, is lost. Finally, we demonstrate that human mdm2 is able to down regulate the transcriptional activity of Xenopus p53.

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“…via Ref1. This is proposed based on the established role of Ref1 in regulation of p53 transcriptional activities depending on the redox status and oxidized state of p53 (Jayaraman et al, 1997). Thus, a Ref1-thioredoxin complex may also participate in the regulation of p53 by ROS.…”

Section: Thioredoxin E Ects On Transcription Factorsmentioning

confidence: 99%

Role of redox potential and reactive oxygen species in stress signaling

et al. 1999

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Stress-activated signaling cascades are a ected by altered redox potential. Key contributors to altered redox potential are reactive oxygen species (ROS) which are formed, in most cases, by exogenous genotoxic agents including irradiation, in¯ammatory cytokines and chemical carcinogens. ROS and altered redox potential can be considered as the primary intracellular changes which regulate protein kinases, thereby serving as an important cellular component linking external stimuli with signal transduction in stress response. The mechanisms, which underlie the ROS-mediated response, involve direct alteration of kinases and transcription factors, and indirect modulation of cysteine-rich redox-sensitive proteins exempli®ed by thioredoxin and glutathione Stransferase. This review summarizes the current understanding of the mechanisms contributing to ROS-related changes in key stress activated signaling cascades.

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Identification of redox/repair protein Ref-1 as a potent activator of p53.

Cited by 441 publications

References 36 publications

Protection of normal human reconstructed epidermis from UV by catalase overexpression

Protection of normal human reconstructed epidermis from UV by catalase overexpression

Regulation of the specific DNA binding activity of Xenopus laevis p53: evidence for conserved regulation through the carboxy-terminus of the protein

Role of redox potential and reactive oxygen species in stress signaling

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