Publicação
Dietary compound resveratrol is a pan-BET bromodomain inhibitor
| Resumo: | The chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100μM increased the melting temperature (ΔTm) of BET bromodomains by around 2.0ᵒC. The micromolar dissociation constant (Kd) range was characterized using Isothermal Titration Calorimetry (ITC). The RSV Kd value accounted to 6.6 μM in case of BRD4(1). Molecular docking proposed the binding mode of RSV against BRD4(1) mimicking the acetyl-lysine interactions. All these results suggest that RSV can also recognize epigenetic readers domains by interacting with BET bromodomains. |
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| Autores principais: | Dutra, Luiz Antonio |
| Outros Autores: | Heidenreich, David; da Silva, Gabriel Dalio Bernardes; Chin, Chung Man; Knapp, Stefan; dos Santos, Jean Leandro |
| Assunto: | Bromodomains Differential Scanning Calorimetry (DSF) Epigenetic Isothermal Titration Calorimetry (ITC) Resveratrol |
| Ano: | 2018 |
| País: | Brasil |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | IBICT |
| Idioma: | inglês |
| Origem: | Oasisbr |
| Resumo: | The chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100μM increased the melting temperature (ΔTm) of BET bromodomains by around 2.0ᵒC. The micromolar dissociation constant (Kd) range was characterized using Isothermal Titration Calorimetry (ITC). The RSV Kd value accounted to 6.6 μM in case of BRD4(1). Molecular docking proposed the binding mode of RSV against BRD4(1) mimicking the acetyl-lysine interactions. All these results suggest that RSV can also recognize epigenetic readers domains by interacting with BET bromodomains. |
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