Table 2:

Recently reported deacetylation substrates of Sirtuins

SIRT1
Type	Substrate	Full name	Modification Sites	Functions	Reference
Transcription Factors	PRRX1	Paired related homeobox 1	K160	Upregulates KLF4 to promote cell sternness and migration through LDH1 upregulation	[122]
	KLF4	Kruppel-like factor 4	Unknown	Regulates the ovarian cancer cell invasion by inducing the expression of Claudin-5	[123]
	NFATcl	Nuclear factor of activated T-cells, cytoplasmic 1	Unknown	Polarization and recruitment of adipose tissue macrophages	[124]
	C/EBPα	CCAAT/enhancer-binding protein alpha	K159, K298	Increases mitochondrial respiration by upregulating mitochondrial genes	[125]
Others	TET2	Tet methylcytosine dioxygenase 2	K1468, K1472, K1473, K1478	Activates TET2 to ameliorate myelodysplastic syndrome	[126]
	MDM2	E3 ubiquitin ligase murine double minute 2	K182, K185	Promotes self-ubiquitination and degradation of MDM2, which stabilizes p53 to promote apoptosis in osteosarcoma	[127]
	DNMT3I	DNA (cytosine-5)-methyltransferase 3-like	Unknown	Destabilizes DNMT3I protein by direct deacetylation to promote ESCs differentiation	[128]
	RPA1	Replication Protein Al	K163	Decreases interaction with XPA during DNA repair	[52]
	PABP1	Poly(A)-binding protein 1	K95	Retains of PABP1 and mRNA in the nucleus inhibiting protein translation	[57]
	9G8	SR protein 9G8	K24	Promotes the inclusion of tau exon 10.	[58]
SIRT2
Histone	H3	Histone H3	K18	Translocates SIRT2 into nucleus to deacetylate H3K18 to reprogram transcription, when Listeria monocytogenes infected	[75]
Transcription Factors	NFAT	Nuclear factor of activated T-cells	unknown	Destabilizes NFATc2 and suppresses its nuclear localization, resulting in decreased transcription activity to cardiac homeostasis	[129]
	NRF2	Nuclear factor erythroid-derived 2-related factor 2	K506, K508	Reduces NRF2 levels, to reduce ferroportin 1 expression and decrease iron export	[130]
	slug	Slug	K116	Stabilizes slug	[73]
	JNK	c-Jun NH2-terminal kinases	K153	Enhances ATP binding and enzymatic activity of JNK towards c-Jun; favors the phosphorylation of JNK by MKK4	[131]
	p73	Tumor suppressor p73	K620, K623, K627	Suppresses its transcriptional activity, critical for tumorigenicity of glioblastoma cells	[74]
Metabolism Enzyme	ALDA	Aldolase	K322	Suppresses glycolytic enzyme activities, and regulates metabolic reprogramming during induced pluripotency	[59]
	ENO1	Enolase	unknown	Suppresses glycolytic enzyme activities, and regulates metabolic reprogramming during induced pluripotency	[59]
	PGK1	Phosphoglycerate Kinase 1	unknown	Suppresses glycolytic enzyme activities, and regulates metabolic reprogramming during induced pluripotency	[59]
	GAPDH	Glyceraldehyde 3-phosphate dehydrogenase	unknown	Suppresses glycolytic enzyme activities, and regulates metabolic reprogramming during induced pluripotency	[59]
	PKM2	M2 isoform of pyruvate kinase	K305	Induces PKM2 activity by promoting tetramerization to the active enzymatic form	[132]
Others	ANKLE2	Ankyrin and LEM domain-containing protein 2	K302	Promotes ANKLE2 phosphorylation and nuclear envelope reassembly	[133]
	ATRIP	ATR-interacting protein	K32	Drives ATRIP phopshorylation and accumulation to DNA damage sites in response to replication stress	[76]
	GSK3	Glycogen synthase kinase 3	K246/K183	Enhances its binding to ATP	[134]
SIRT6
Histone	H3	Histone H3	K9	Silences Notch1/4, suppresses Notch signaling in podocytes	[86]
	H3	Histone H3	K9	Allows ADP-ribosylation in response to DNA damage	[98]
	H3	Histone H3	K56	Silences IGFBP2, activates AKT signaling in melanoma cell	[87]
	H3	Histone H3	K56	Promotes ATF4 destabilization from target genes	[92]
	H3	Histone H3	K9, K56	Silences LIN28b, suppresses let-7 target genes in pancreatic cancer	[88]
	H3	Histone H3	K9, K56	Transcriptionally suppresses long non-coding RNAH19	[89]
	H3	Histone H3	K9, K56	Silences pluripotency genes in embryonic stem cells	[90]
Transcription Factors	p53	Tumor suppressor 53	K381	Destabilizes p53	[94]
	PKM2	Pyruvate kinase M2 (nuclear)	K433	Leads to nuclear export of nuclear PKM2, suppressing its transcription activity in hepatocellular carcinoma	[95]
Others	TRF2	Telomere repeat binding factor 2	K176, K179, K190	Destabilizes TRF2 in response to DNA damage	[97]
SIRT7
Transcription Factors	SP7/OSX	Osterix	K368	Promotes its transactivation activity in bone formation	[135]
Others	DDX21	DEAD-box RNA helicase	K18, K137, K600	Augments helicase activity and overcomes R-loop-mediated stalling of RNA polymerases, safeguards genome stability	[117]