HADC5 deacetylates MKL1 to dampen TNF-α induced proinflammatory gene transcription in macrophages

Zilong Li, Hao Qin, Jianfei Li, Liming Yu, Yuyu Yang, Yong Xu

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Macrophage-dependent inflammatory response on the one hand functions as a key line of defense in host immunity but on the other hand underlies the pathogenesis of a host of human pathologies when aberrantly activated. Our previous investigations have led to the identification of megakaryocytic leukemia 1 (MKL1) as a key cofactor of NF-κB/p65 participating in TNF-α induced pro-inflammatory transcription in macrophages. How post-translational modifications contribute to the modulation of MKL1 activity remains an underexplored subject matter. Here we report that the lysine deacetylase HDAC5 interacts with and deacetylates MKL1 in cells. TNF-α treatment down-regulates HDAC5 expression and expels HDAC5 from the promoters of pro-inflammatory genes in macrophages. In contrast, over-expression of HDAC5 attenuates TNF-α induced pro-inflammatory transcription. Mechanistically, HDAC5- mediated MKL1 deacetylation disrupts the interaction between MKL1 and p65. In addition, deacetylation of MKL1 by HDAC5 blocks its nuclear translocation in response to TNF-α treatment. In conclusion, our work has identified an important pathway that contributes to the regulation of pro-inflammatory response in macrophages.

Original languageEnglish (US)
Pages (from-to)94235-94246
Number of pages12
Issue number55
StatePublished - Nov 1 2017
Externally publishedYes


  • Deacetylation
  • HDAC5
  • MKL1
  • Post-translational modification
  • Transcriptional regulation

ASJC Scopus subject areas

  • Oncology


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