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<b>Abstract</b>— <p>The transcription factor NRF2 is one of the key components that provide cellular protection against damage. Its activity is associated with other signaling pathways that can have both direct and indirect effects on it. These include the proteins that, like p300/CBP and HDACs, can affect the NRF2 activity through acetylation and deacetylation. However, studies from different research groups sometimes contradict each other. On the one hand, there are data evidencing that acetylation increases the NRF2 activity, while deacetylation decreases its activity. On the other hand, it was demonstrated that activation of SIRT1 deacetylase increased post-translational activity of NRF2. At the same time, NRF2 itself can affect SIRT1 expression, forming a positive feedback loop. This review discusses different aspects of the interaction between the transcription factor NRF2 activity and acetylases/deacetylases, primarily SIRT1. In addition, indirect interactions between NRF2 and SIRT1 via other signaling pathways associated with PGC-1α and p62 are considered.</p>

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Regulation of the NRF2 Transcription Factor Activity by SIRT1-Induced Deacetylation: A Possible SIRT1–NRF2 Feedback Loop

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • A. P. Gureev,
  • E. P. Krutskikh

摘要

Abstract—

The transcription factor NRF2 is one of the key components that provide cellular protection against damage. Its activity is associated with other signaling pathways that can have both direct and indirect effects on it. These include the proteins that, like p300/CBP and HDACs, can affect the NRF2 activity through acetylation and deacetylation. However, studies from different research groups sometimes contradict each other. On the one hand, there are data evidencing that acetylation increases the NRF2 activity, while deacetylation decreases its activity. On the other hand, it was demonstrated that activation of SIRT1 deacetylase increased post-translational activity of NRF2. At the same time, NRF2 itself can affect SIRT1 expression, forming a positive feedback loop. This review discusses different aspects of the interaction between the transcription factor NRF2 activity and acetylases/deacetylases, primarily SIRT1. In addition, indirect interactions between NRF2 and SIRT1 via other signaling pathways associated with PGC-1α and p62 are considered.