Acetylation of HDAC1 and degradation of SIRT1 form a positive feedback loop to regulate p53 acetylation during heat-shock stress

H. Yang, B. Yan, D. Liao, S. Huang, Y. Qiu

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43 Scopus citations


The tumor suppressor p53 is an essential transcription factor that sensitively regulates cellular responses to various stresses. Acetylation, a critically important posttranslational modification of p53, is induced in response to cellular stresses. P53 acetylation level strongly correlates with protein stability and activity. The steady-state level of p53 acetylation is balanced by dynamic acetylation and deacetylation. Despite the function of p53 acetylation being well studied, how the steady state of p53 acetylation level is regulated in response to cellular stresses remains unclear. In particular, the dynamic regulation of the deacetylase activities responsible for p53 deacetylation during cellular stress is unknown. In the current study, we investigated the dynamic regulation of HDAC1 (histone deacetylase 1) and SIRT1 (sirtuin 1), two major enzymes for p53 deacetylation, during cell stress. We found that various cell stress events induce HDAC1 acetylation. The increased level of HDAC1 acetylation correlates with the level of p53 acetylation. Acetylated HDAC1 loses the ability to deacetylate p53. Cellular stresses also promote the decline of the SIRT1 protein in a proteasome-dependent pathway, which also results in the increase of p53 acetylation. Importantly, the decreased level of SIRT1 also contributes to the accumulation of HDAC1 acetylation as SIRT1 deacetylates HDAC1. Therefore, the increase of HDAC1 acetylation and reduced level of SIRT1 protein during cellular stress directly link to the induction of p53 acetylation. These results unveil the mechanism underlying the dynamic regulation of p53 acetylation during cell stress.

Original languageEnglish (US)
JournalCell Death and Disease
Issue number5
StatePublished - May 1 2015

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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