Schaefer, Claudia and Goeder, Anja and Beyer, Mandy and Kiweler, Nicole and Mahendrarajah, Nisintha and Rauch, Anke and Nikolova, Teodora and Stojanovic, Natasa and Wieczorek, Martin and Reich, Thomas R. and Tomicic, Maja T. and Linnebacher, Michael and Sonnemann, Juergen and Dietrich, Sascha and Sellmer, Andreas and Mahboobi, Siavosh and Heinzel, Thorsten and Schneider, Guenter and Kraemer, Oliver H. (2017) Class I histone deacetylases regulate p53/NF-kappa B crosstalk in cancer cells. CELLULAR SIGNALLING, 29. pp. 218-225. ISSN 0898-6568, 1873-3913
Full text not available from this repository. (Request a copy)Abstract
The transcription factors NF-kappa B and p53 as well as their crosstalk determine the fate of tumor cells upon therapeutic interventions. Replicative stress and cytolcines promote signaling cascades that lead to the co-regulation of p53 and NF-kappa B. Consequently, nuclear p53/NF-kappa B signaling complexes activate NF-kappa B-dependent survival genes. The 18 histone deacetylases (HDACs) are epigenetic modulators that fall into four classes (I-IV). Inhibitors of histone deacetylases (HDACi) become increasingly appreciated as anti-cancer agents. Based on their effects on p53 and NF-kappa B, we addressed whether clinically relevant HDACi affect the NF-kappa B/p53 crosstalk. The chemotherapeutics hydroxyurea, etoposide, and fludarabine halt cell cycle progression, induce DNA damage, and lead to DNA fragmentation. These agents co-induce p53 and NF-kappa B-dependent gene expression in cell lines from breast and colon cancer and in primary chronic lymphatic leukemia (CLL) cells. Using specific HDACi, we find that the class I subgroup of HDACs, but not the class lib deacetylase HDAC6, are required for the hydroxyurea-induced crosstalk between p53 and NF-kappa B. HDACi decrease the basal and stress-induced expression of p53 and block NF-kappa B-regulated gene expression. We further show that class I HDACi induce senescence in pancreatic cancer cells with mutant p53. (C) 2016 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; MUTANT P53; VALPROIC ACID; REPLICATION STRESS; COLORECTAL-CANCER; GENE-EXPRESSION; HDAC INHIBITORS; APOPTOSIS; HDAC; HDACi; NF-kappa B; p53; Replicative stress; Survivin |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 12:58 |
| Last Modified: | 18 Feb 2019 14:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/152 |
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