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Author Notes:

Jin-Tang Dong (j.dong@emory.edu).

R.T. designed and performed experiments, and analyzed the data; B.Z. designed and performed some experiments, and wrote the manuscript.

Y.L. performed some analyses.

J.L.K., R.T., S.X. and C.S. designed some experiments, provided comments, and edited the manuscript; and J.T.D. conceived the idea, designed some of the experiments, provided overall guidance, and wrote and finalized the manuscript.

We thank Dr. Anthea Hammond for copy editing the manuscript.


Research Funding:

This work was supported by grant R01CA171189 from the National Cancer Institute; National Institutes of Health; and grant 81130044 from the National Natural Science Foundation of China.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Biophysics
  • KLF5
  • Acetylation
  • Histone deacetylases (HDACs)
  • Protein stability
  • P21

HDAC-mediated deacetylation of KLF5 associates with its proteasomal degradation


Journal Title:

Biochemical and Biophysical Research Communications


Volume 500, Number 3


, Pages 777-782

Type of Work:

Article | Post-print: After Peer Review


Krüppel-like factor 5 (KLF5) is a basic transcription factor that regulates diverse cellular processes during tumor development. Acetylation of KLF5 at lysine 369 (K369) reverses its function from promoting to suppressing cell proliferation and tumor growth. In this study, we examined the regulation of KLF5 by histone deacetylases in the prostate cancer cell line DU 145. While confirming the functions of HDAC1/2 in KLF5 deacetylation and the promotion of cell proliferation, we found that the knockdown of HDAC1/2 upregulated KLF5 protein but not KLF5 mRNA, and the increase in KLF5 protein level by silencing HDAC1/2 was at least in part due to decreased proteasomal degradation. Deacetylase activity was required for HDAC1/2-mediated KLF5 degradation, and mutation of KLF5 to an acetylation-mimicking form prevented its degradation, even though the mutation did not affect the binding of KLF5 with HDAC1/2. Mutation of K369 to arginine, which prevents acetylation, did not affect the binding of KLF5 to HDAC1 or the response of KLF5 to HDAC1/2-promoted degradation. These findings provide a novel mechanistic association between the acetylation status of KLF5 and its protein stability. They also suggest that maintaining KLF5 in a deacetylated form may be an important mechanism by which KLF5 and HDACs promote cell proliferation and tumor growth.

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© 2019 Elsevier B.V. or its licensors or contributors

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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