Histone deacetylase modulators provided by Mother Nature

Genes & Nutrition

Table 1 Presentation of the different HDAC isoforms

HDAC		Cellular localization	Substrates
Class	Member	Cellular localization	Substrates
I	HDAC1	Nucleus	Histones, DNMT1, SHP, ATM, MEF2, MyoD, p53, NF-κB, AR, BRCA1, MECP2, pRb
	HDAC2	Nucleus	Histones, NF-κB, GATA2, BRCA1, pRb, MECP
	HDAC3	Nucleus	Histones, HDAC4, 5, 7 et 9, SHP, GATA1, NF-κB, pRb
	HDAC8	Mainly in the nucleus	HSP70
IIa	HDAC4	Nucleocytoplasmic traffic	Histones, HDAC3, MEF2, CaM, 14-3-3
	HDAC5	Nucleocytoplasmic traffic	Histones, HDAC3, MEF2, CaM, 14-3-3
	HDAC7	Nucleocytoplasmic traffic	Histones, HDAC3, MEF2, CaM, 14-3-3, HIF-1α
	HDAC9	Nucleus	Histones, HDAC3, MEF2, CaM, 14-3-3
IIb	HDAC6	Mainly in the cytoplasm	HDAC11, SHP, PP1, α-tubulin, HSP90
	HDAC10	Nucleus and cytoplasm	LcoR, PP1
III	SIRT1	Mainly in the nucleus	FOXO, p53, p300, NF-κB, histones
	SIRT2	Nucleus and cytoplasm	Histone H4, α-tubulin, PPAR-γ, FOXO, p53, p300
	SIRT3^b	Mitochondria	PGC-1α, FOXO, p53, Ku70, Acetyl-CoA synthetase 2, complex I
	SIRT4^a	Mitochondria	Glutamate dehydrogenase
	SIRT5	Mitochondria	Cytochrome c, carbamoyl phosphate synthetase 1
	SIRT6^b	Nucleus	Histone H3, TNF-α
	SIRT7	Mainly in the nucleus	p53, RNA polymerase I
IV	HDAC11	Nucleus	HDAC6

AR androgen receptor, ATM ataxia-telangiectasia-mutated, BRCA breast cancer, CaM calmodulin, CoA co-enzyme A, DNMT DNA methyltransferase, FOXO forkhead box O, GATA GATA binding protein, HDAC histone deacetylase, HIF hypoxia-inducible factor, HSP heat shock protein, LcoR ligand-dependent receptor co-repressor, MECP methyl-CpG-binding domain protein, MEF myocyte enhancer factor, NF-κB nuclear transcription factor-kappa B, PGC peroxisome proliferator-activated receptor gamma coactivator, PP1 protein phosphatase, PPAR peroxisome proliferator-activated receptor, pRb retinoblastoma protein, SHP Src homology region 2-domain-containing phosphatase, SIRT sirtuin, TNF tumor necrosis factor
^aSIRT4 is an ADP-ribosyltransferase and lacks deacetylase activity
^bSIRT3 and 6 possess, in addition to their deacetylase activity, the ADP-ribosyltransferase activity (adapted from Folmer et al. 2010)

ISSN: 1865-3499