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)

Ref-1 is a nuclear protein that possesses DNA repair activity and has a role in the redox activation of Fos and Jun transcription factors. Using an antibody to Ref-1 we investigated the expression and distribution of this protein in the adult rat brain. Ref-1 was located in the nucleus of neurons and glial fibrillary acidic protein-positive astrocytes throughout the brain. Levels were particularly high in granule cells of the dentate gyrus, piriform cortex neurons, and Purkinje cells of the cerebellum, and lower in CA1 pyramidal cells, striatal neurons, and the neurons of the neocortex. These results suggest that the action of inducible transcription factors such as c-Jun in mammalian neurons is likely to be regulated by constitutively expressed Ref-1, in particular in dentate granule cells. The high levels of Ref-1 in glial fibrillary acidic protein-positive astrocytes suggest that it may also modulate the action of inducible transcription factors in these cells, particularly after brain injury. The possibility also exists that Ref-1 may primarily function as a DNA repair enzyme in brain cells.
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PMID:Ref-1 expression in adult mammalian neurons and astrocytes. 764 43

Arsenite is a human carcinogen causing skin, bladder, and lung tumors, but the cellular mechanisms underlying these effects remain unclear. We investigated expression of the essential base excision DNA repair enzyme apurinic endonuclease 1 (Ape1) in response to sodium arsenite. In mouse 10T(1/2) fibroblasts, Ape1 induction in response to arsenite occurred about equally at the mRNA, protein, and enzyme activity levels. Analysis of the APE1 promoter region revealed an AP-1/CREB binding site essential for arsenite-induced transcriptional activation in both mouse and human cells. Electrophoretic mobility shift assays indicated that an ATF4/c-Jun heterodimer was the responsible transcription factor. RNA interference targeting c-Jun or ATF4 eliminated arsenite-induced APE1 transcription. Suppression of Ape1 or ATF4 sensitized both mouse fibroblasts (10T(1/2)) and human lymphoblastoid cells (TK6) to arsenite cytotoxicity. Expression of Ape1 from a transgene did not efficiently restore arsenite resistance in ATF4-depleted cells but did offset initial accumulation of abasic DNA damage following arsenite treatment. Mutagenesis by arsenite (at the TK and HPRT loci in TK6 cells) was observed only for ATF4-depleted cells, which was strongly offset by Ape1 expression from a transgene. Therefore, the ATF4-mediated up-regulation of Ape1 and other genes plays a key role against arsenite-mediated toxicity and mutagenesis.
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PMID:ATF4-dependent oxidative induction of the DNA repair enzyme Ape1 counteracts arsenite cytotoxicity and suppresses arsenite-mediated mutagenesis. 1793 2