title: The acetyltransferase HAT1 moderates the NF-κB response by regulating the transcription factor PLZF.
abstract: 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-α 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-κB p50 subunit that limits the NF-κB 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-κB transcriptional programme.
authors: 1] Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia [2] Department of Molecular and Translational Science, Monash University, Melbourne, Victoria 3168, Australia.
authors: Anthony J
authors: AJ
authors: Sadler
authors: Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia.
authors: Bandar A
authors: BA
authors: Suliman
authors: 1] Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia [2] Department of Molecular and Translational Science, Monash University, Melbourne, Victoria 3168, Australia.
authors: Liang
authors: L
authors: Yu
authors: Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors: Xiangliang
authors: X
authors: Yuan
authors: 1] Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia [2] Department of Molecular and Translational Science, Monash University, Melbourne, Victoria 3168, Australia.
authors: Die
authors: D
authors: Wang
authors: Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia.
authors: Aaron T
authors: 0000000201961570
authors: AT
authors: Irving
authors: Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia.
authors: Soroush T
authors: ST
authors: Sarvestani
authors: 1] Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia [2] Department of Molecular and Translational Science, Monash University, Melbourne, Victoria 3168, Australia.
authors: Ashish
authors: A
authors: Banerjee
authors: 1] Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia [2] Department of Molecular and Translational Science, Monash University, Melbourne, Victoria 3168, Australia.
authors: Ashley S
authors: AS
authors: Mansell
authors: Institute of Ageing Research, Hangzhou Normal University School of Medicine, 1378 Wenyi Road West, Hangzhou, Zhejiang 311121, China.
authors: Jun-Ping
authors: JP
authors: Liu
authors: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University Clayton Campus, Wellington Road, Clayton, Victoria 3800, Australia.
authors: Steve
authors: S
authors: Gerondakis
authors: 1] Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia [2] Department of Molecular and Translational Science, Monash University, Melbourne, Victoria 3168, Australia.
authors: Bryan R G
authors: BR
authors: Williams
authors: 1] Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia [2] Department of Molecular and Translational Science, Monash University, Melbourne, Victoria 3168, Australia [3] Institute of Ageing Research, Hangzhou Normal University School of Medicine, 1378 Wenyi Road West, Hangzhou, Zhejiang 311121, China.
authors: Dakang
authors: D
authors: Xu
mesh_terms: D000107:Acetylation; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000276:immunology; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000276:immunology; D006655:Histone Deacetylases / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011499:Protein Processing, Post-Translational; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D051741:Kruppel-Like Transcription Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D018124:Receptors, Tumor Necrosis Factor; D000099186:Histone Deacetylase 3; C513267:Zbtb16 protein, mouse; C110880:histone acetyltransferase type B complex; C517671:Camk2a protein, mouse