Acetylation of MKL1 by PCAF regulates pro-inflammatory transcription

作者：Yu, Liming; Li, Zilong; Fang, Mingming; Xu, Yong^*

来源：Biochimica et Biophysica Acta-Gene Regulatory Mechanisms, 2017, 1860(8): 839-847.

DOI：10.1016/j.bbagrm.2017.05.006

• Transcriptional regulation
• MKL1
• PCAF
• Acetylation

Inflammation is considered a fundamental host defense mechanism and, when aberrantly activated, contributes to a host of human diseases. Previously we have reported that the transcriptional regulator megakaryocytic leukemia 1 (MKL1) plays a role programming cellular inflammatory response by modulating NF-kappa B activity. Here we report that MKL1 was acetylated in vivo and pro-inflammatory stimuli (TNF-alpha and LPS) augmented MKL1 acetylation accompanying increased MKL1 binding to NF-kappa B target promoters. Further analysis revealed that the lysine acetyltransferase PCAF mediated MKL1 acetylation: TNF-alpha and LPS promoted the interaction between MKL1 and PCAF whereas depletion of PCAF abrogated the induction of MKL1 acetylation by TNF-alpha and LPS. Acetylation of MKL1 was necessary for MKL1 to activate the transcription of pro-inflammatory genes because mutation of four conserved lysine residues in MKL1 attenuated its capacity as a trans-activator of NF-kappa B target genes. Mechanistically, MKL1 acetylation served to promote MKL1 nuclear enrichment, to enhance the MKL1-NF-kappa B interaction, and to stabilize the binding of MKL1 on target promoters. In conclusion, our data unveil an important pathway that contributes to the transcriptional regulation of inflammatory response.

• 出版日期2017-8
• 单位南京医科大学; 江苏建康职业学院