Beyond Histone and Deacetylase: An Overview of Cytoplasmic Histone Deacetylases and Their Nonhistone Substrates

Table 4

Cytoplasmic sirtuins, their substrates in the cytoplasm, and their functions.

Mammalian cytoplasmic sirtuins	Substrates	Functions	Comments
SIRT1 (subcellular localization is cell type dependent)		Cytoplasmic localization of SIRT1 is linked to apoptosis	Whether SIRT1 enhances or decreases apoptosis and the mechanistic details remain unclear
SIRT2 (shuttles between nucleus and cytoplasm)	α-tubulin	Mitotic exit of normal cell cycle; Regulation of mitotic checkpoint under stress; Neuronal motility and differentiation	Subcellular localization of SIRT2 modifications that modulate deacetylase activity of SIRT2, namely, phosphorylation and acetylation, is largely unspecified; Mechanism(s) through which SIRT2 regulates mitotic exit remains unclear
SIRT3; (in mitochondria)	AceCS2; GDH; ICDH2; Complex I of electron transport chain; Ku70; Nampt; MRPL10	Regulation of energy metabolism and apoptosis	GDH activity is not significantly altered in Sirt3 knockout mice
SIRT4; (in mitochondria)	GDH; (SIRT4 also interacts with ANT2, SIRT3, and IDE)	Regulation of insulin secretion	SIRT4 is an ADP ribosylase; No deacetylase activity is reported for SIRT4; ADP-ribosylation of ANT2, SIRT3, or IDE by SIRT4 has not been shown definitely
SIRT5; (in mitochondria)	CPS1 cytochrome c	Regulation of urea cycle; Promotes apoptosis?	Exact submitochondrial localization of SIRT5, how calorie restriction alters CPS1 acetylation through SIRT5, and what lysines in CPS1 are acetylated under different nutrient availability remain controversial