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HADC5 deacetylates MKL1 to dampen TNF-? induced pro-inflammatory gene transcription in macrophages.

ABSTRACT: 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 co-factor of NF-?B/p65 participating in TNF-? 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-? 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-? 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-? treatment. In conclusion, our work has identified an important pathway that contributes to the regulation of pro-inflammatory response in macrophages.

SUBMITTER: Li Z

PROVIDER: S-EPMC5706870 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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HADC5 deacetylates MKL1 to dampen TNF-α induced pro-inflammatory gene transcription in macrophages.

Li Zilong Z Qin Hao H Li Jianfei J Yu Liming L Yang Yuyu Y Xu Yong Y

Oncotarget 20171009 55

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 co-factor of NF-κB/p65 participating in TNF-α induced pro-inflammatory transcription in macrophages. How post-translational modifications contribute to the modulation of MKL1 act ...[more]

PMID: 29212224

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Dataset Information

HADC5 deacetylates MKL1 to dampen TNF-? induced pro-inflammatory gene transcription in macrophages.

Publications

HADC5 deacetylates MKL1 to dampen TNF-α induced pro-inflammatory gene transcription in macrophages.

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