TY - JOUR
T1 - The acetyltransferase HAT1 moderates the NF-?B response by regulating the transcription factor PLZF
AU - Sadler, Anthony John
AU - Suliman, Bandar Ali
AU - Yu, Liang
AU - Yuan, Xiang-Liang
AU - Wang, Die
AU - Irving, Aaron Trent
AU - Sarvestani, Soroush
AU - Banerjee, Ashish
AU - Mansell, Ashley Scott
AU - Liu, Jun-Ping
AU - Gerondakis, Steven Demetrious
AU - Williams, Bryan Raymond George
AU - Xu, Dakang
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.nature.com/ncomms/2015/150413/ncomms7795/pdf/ncomms7795.pdf
U2 - 10.1038/ncomms7795
DO - 10.1038/ncomms7795
M3 - Article
SN - 2041-1723
VL - 6
SP - 1
EP - 11
JO - Nature Communications
JF - Nature Communications
IS - 13 (Art. ID: 6795)
ER -