Informace o publikaci
Redox state of p63 and p73 core domains regulates sequence-specific DNA binding
| Autoři | |
|---|---|
| Rok publikování | 2013 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Biochemical and biophysical research communications |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.1016/j.bbrc.2013.02.097 |
| Obor | Genetika a molekulární biologie |
| Klíčová slova | p53 protein family; Tumor suppressor; Sequence-specific DNA binding; Redox state; EMSA; Zinc; Cysteine; Transcription factor; Oxidative stress |
| Popis | Cysteine oxidation and covalent modification of redox sensitive transcription factors including p53 are known, among others, as important events in cell response to oxidative stress. All p53 family proteins p53, p63 and p73 act as stress-responsive transcription factors. Oxidation of p53 central DNA binding domain destroys its structure and abolishes its sequence-specific binding by affecting zinc ion coordination at the protein-DNA interface. Proteins p63 and p73 can bind the same response elements as p53 but exhibit distinct functions. Moreover, all three proteins contain highly conserved cysteines in central DNA binding domain suitable for possible redox modulation. In this work we report for the first time the redox sensitivity of p63 and p73 core domains to a thiol oxidizing agent azodicarboxylic acid bis[dimethylamide] (diamide). Oxidation of both p63 and p73 abolished sequence-specific binding to p53 consensus sequence, depending on the agent concentration. In the presence of specific DNA all p53 family core domains were partially protected against loss of DNA binding activity due to diamide treatment. Furthermore, we detected conditional reversibility of core domain oxidation for all p53 family members and a role of zinc ions in this process. We showed that p63 and p73 proteins had greater ability to resist the diamide oxidation in comparison with p53. Our results show p63 and p73 as redox sensitive proteins with possible functionality in response of p53 family proteins to oxidative stress. (C) 2013 Elsevier Inc. All rights reserved. |