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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Endo, Akiko Sumi, Daigo Iwamoto, Noriko Kumagai, Yoshito |
| Description | Country affiliation: Japan Author Affiliation: Endo A ( Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.) |
| Abstract | 1,2-Naphthoquinone (1,2-NQ) is an atmospheric electrophile that reacts covalently with protein thiols. Our previous study revealed that exposure of bovine aortic endothelial cells to 1,2-NQ causes covalent modification of cAMP response element-binding protein (CREB), thereby inhibiting its DNA binding activity and substantial gene expression of B-cell lymphoma-2 (Bcl-2) that is regulated by this transcription factor. In this study, we identified the modification sites of CREB that are associated with the decreased transcriptional activity. Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis indicated that three amino acids (Cys-286, Lys-290, and Lys-319) were irreversibly modified by 1,2-NQ. Mutational analysis revealed that electrophilic modification of Cys-286, but not the other two amino acids, at the DNA binding domain is essential for the reduced CREB activity. Substitution of Cys-286 with tryptophan (C286W), which mimics CREB modification by 1,2-NQ, supported this notion. These results suggest that the covalent interaction of CREB with 1,2-NQ through Cys-286 blocks the DNA binding activity of CREB, resulting in the repression of CREB-regulated genes. |
| File Format | HTM / HTML |
| ISSN | 00092797 |
| Issue Number | 3 |
| Volume Number | 192 |
| e-ISSN | 18727786 |
| Journal | Chemico-Biological Interactions |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2011-07-15 |
| Publisher Place | Ireland |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Discipline Pharmacology Cyclic Amp Response Element-binding Protein Genetics Cysteine Metabolism Environmental Pollutants Toxicity Naphthoquinones Cell Line, Tumor Gene Expression Drug Effects Gene Expression Regulation, Neoplastic Humans Mutagens Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Toxicology |
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