The acetyltransferase HAT1 moderates the NF-?B response by regulating the transcription factor PLZF

Anthony John Sadler, Bandar Ali Suliman, Liang Yu, Xiang-Liang Yuan, Die Wang, Aaron Trent Irving, Soroush Sarvestani, Ashish Banerjee, Ashley Scott Mansell, Jun-Ping Liu, Steven Demetrious Gerondakis, Bryan Raymond George Williams, Dakang Xu

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60 Citations (Scopus)


To date, the activities of protein kinases have formed the core of our understanding of cell signal transduction. Comprehension of the extent of protein acetylation has raised expectations that this alternate post-transcriptional modification will be shown to rival phosphorylation in its importance in mediating cellular responses. However, limited instances have been identified. Here we show that signalling from Toll-like or TNF-alpha receptors triggers the calcium/calmodulin-dependent protein kinase (CaMK2) to activate histone acetyltransferase-1 (HAT1), which then acetylates the transcriptional regulator PLZF. Acetylation of PLZF promotes the assembly of a repressor complex incorporating HDAC3 and the NF-kappaB p50 subunit that limits the NF-kappaB response. Accordingly, diminishing the activity of CaMK2, the expression levels of PLZF or HAT1, or mutating key residues that are covalently modified in PLZF and HAT1, curtails control of the production of inflammatory cytokines. These results identify a central role for acetylation in controlling the inflammatory NF-kappaB transcriptional programme.
Original languageEnglish
Pages (from-to)1 - 11
Number of pages11
JournalNature Communications
Issue number13 (Art. ID: 6795)
Publication statusPublished - 2015

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