The phosphorylation to acetylation/methylation cascade in transcriptional regulation: how kinases regulate transcriptional activities of DNA/histone-modifying enzymes

Zhao, Pin; Malik, Samiullah

doi:10.1186/s13578-022-00821-7

Table 3 Phosphorylation of histone deacetylases (HDAC1-11) and its effect on the enzymatic activity

From: The phosphorylation to acetylation/methylation cascade in transcriptional regulation: how kinases regulate transcriptional activities of DNA/histone-modifying enzymes

Isoforms of KMTs	Target residues	Kinases	Functional regulation upon phosphorylation	Involved in diseases and signaling pathways	References
HDAC1	Thr65	CaMKII	Activation of enzymatic activity	Heart failure	[163]
	Ser69
	Ser85
	Thr195
	Ser197
	Thr355
	Tyr72	EGFR	Stabilization	Cancer cell survival	[134]
	Ser406	Aurora A/B	Activation of enzymatic activity	Zebrafish embryos development	[133]
	Ser423	CK2	Enhance of its interaction with SIN3A	Cell cycle	[164]
	Ser421	CK2	Enhance of its interaction with SIN3A	Cell cycle	[164]
	Ser421	NLK	Disruption of its interaction with LEF1	WNT signaling pathway	[131]
HDAC2	Ser407	CK2	Disruption of its interaction with RARα	Proliferation of vascular smooth muscle cells	[137]
	Ser394	CK2	Inhibition of enzymatic activity	Inflammation	[136]
	Ser422
	Ser424
HDAC3	Ser374	CaMKII	Inhibition of enzymatic activity	Heart failure	[144, 163]
	Ser374	HIPK2	Inhibition of enzymatic activity	Colorectal carcinoma and sepsis	[144]
	Ser424	CK2	Activation of enzymatic activity	Tumorigenesis	[139]
		TBK1	Activation of enzymatic activity	Innate antiviral immunity	[140]
		LRRK2	Activation of enzymatic activity	Parkinson’s disease	[140]
		c-Jun N-terminal kinase	Activation of enzymatic activity	Triple-negative breast cancer	[142]
		PINK1	Activation of enzymatic activity	Parkinson’s disease	[143]
HDAC4	Ser246	TBK1/IKKε	Suppression of IRF3 phosphorylation	Innate immune	[165]
		CaMKIV	Enhance of its interaction with 14-3-3	DNA binding	[166]
		PKD	Nuclear extrusion into the cytoplasm	Mitogenic signaling	[167]
		CaMKII	Disruption of its interaction with MEF2	Skeletal muscle hypertrophy	[148]
	Ser467	CaMKIV	Enhance of its interaction with 14-3-3	DNA binding	[166]
	Ser467	CaMKII	Nuclear extrusion into the cytoplasm	Metabolism	[149]
	Ser632	CaMKIV	Enhance of its interaction with 14-3-3	DNA binding	[166]
		PKD	Nuclear extrusion into the cytoplasm	Mitogenic signaling	[167]
		PP2A	Nuclear extrusion into the cytoplasm	Neurodegeneration	[168]
	Ser740	PKA	Stabilization	Bone and chondrocyte development	[151]
HDAC5	Ser259	AMPK	Nuclear extrusion into the cytoplasm	WNT signaling pathway	[155]
		PKD	Enhance of its interaction with 14-3-3	Cardiac myocyte hypertrophy	[153]
		AKT	Nuclear extrusion into the cytoplasm	Vascular disorders	[155]
		CaMKII	Nuclear extrusion into the cytoplasm	Diabetes	[156]
		SIK1	Chromatin remodeling	Cardiac hypertrophy	[169]
		PKCδ	Nuclear extrusion into the cytoplasm	Heart failure	[170]
	Ser280	PKA	Disruption of its interaction with 14-3-3	cAMP/PKA signaling pathway	[171]
	Thr292	PRK1	Disruption of its interaction with 14-3-3		[172]
	Ser493	GRK5	Nuclear extrusion into the cytoplasm	Heart failure; NF-κB signaling pathway	[173]
	Ser498	AMPK	Nuclear extrusion into the cytoplasm	WNT signaling pathway	[154]
		PKD	Enhance of its interaction with 14-3-3	Cardiac myocyte hypertrophy	[153]
		AKT	Nuclear extrusion into the cytoplasm	Vascular disorders-	[155]
		PKA	Nuclear extrusion into the cytoplasm	Heart failure	[174]
	Tyr642	FAK	Nuclear extrusion into the cytoplasm	Osteocyte mechanotransduction	[174]
	Ser661	PKA	Nuclear extrusion into the cytoplasm	Heart failure	[170]
	Ser611	Unknown	Enhance of its interaction with other proteins	Cell cycle	[175]
	Ser755
	Ser1108
HDAC6	Ser21	GRK5	Activation of enzymatic activity	Cancer	[158]
	Ser22	GSK3β	Activation of enzymatic activity	Parkinson’s disease	[159]
	Ser289	ASK1	Stabilization	Retinopathy of prematurity	[176]
	Thr293	ASK1	Stabilization	Retinopathy of prematurity	[176]
	Ser458	CK2	Activation of enzymatic activity	Aggregation of misfolded proteins	[160]
	Tyr570	EGFR	Inhibition of enzymatic activity	Receptor endocytosis and degradation	[162]
	Ser1031	ERK1		Cell migration	[161]
	Ser1035	ERK1	Activation of enzymatic activity	Cell migration	[161]
HDAC7	Ser155	PKD1	Nuclear extrusion into the cytoplasm	Apoptosis	[177]
	Ser178	PKD1	Nuclear extrusion into the cytoplasm	Cell proliferation and migration; VEGF signaling pathway	[178]
		CaMKI	Nuclear extrusion into the cytoplasm	Angiogenesis	[179]
		CRM1	Nuclear extrusion into the cytoplasm	Myogenesis	[180]
	Ser181	PKD1	Nuclear extrusion into the cytoplasm	Bone formation and maintenance	[181]
	Ser318	PKD1	Nuclear extrusion into the cytoplasm	Apoptosis	[180]
	Ser344	PKD1	Nuclear extrusion into the cytoplasm	Cell proliferation and migration; VEGF signaling pathway	[177]
	Ser344	CaMK I	Nuclear extrusion into the cytoplasm	Angiogenesis	[178]
	Ser448	PKD1	Nuclear extrusion into the cytoplasm	Apoptosis	[180]
	Ser479	PKD1	Nuclear extrusion into the cytoplasm	Cell proliferation and migration; VEGF signaling pathway	[181]
	Ser479	CaMKI	Nuclear extrusion into the cytoplasm	Angiogenesis	[177]
HDAC8	Ser39	AMPK	Nuclear extrusion into the cytoplasm	Lung cancer cell survival	[147]
	Ser39	PKA	Inhibition of enzymatic activity		[182]
	Ser43	AMPK	Nuclear extrusion into the cytoplasm	Lung cancer cell survival	[147]
	Ser63	AMPK	Nuclear extrusion into the cytoplasm	Lung cancer cell survival	[147]
HDAC9	Ser218	PKD	Disruption of its interaction with 14-3-3	Cardiac hypertrophy	[152]
HDAC9	Ser448	PKD	Disruption of its interaction with 14-3-3	Cardiac hypertrophy	[152]

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ISSN: 2045-3701

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