Table 1. Mechanism of HDAC Interactors Involved in AD and PD Pathogenesis in Acetylation, Ubiquitination, and SUMOylation.

HDAC interactor	acetylation	ubiquitination	SUMOylation
NPM1	NPM1 acetylation through p300 modulates its subcellular localization and promotes its binding with transcriptionally active RNA polymerase II21	impaired BRCA1-BARD1 ubiquitin ligase causes NPM1 downregulation through p-STAT5, which in turn enhances cell survival22	ARF and TRIM28 coexpression enhances NPM1 SUMOylation and alters its centrosomal localization, which suppressed the centrosome amplification23
HIF1A	acetylation of HIF1A at K709 through p300 increases its stability and decreases polyubiquitination24	HIF1A ubiquitination at K63 through STUB1 causes its proteasomal degradation25	SUMOylation of HIF1A changes its turnover rate through E3 SUMO ligase, which reduces its transcriptional activity26
CASP8	HDAC inhibitor increases Ku70 acetylation and thus decreases FLIP/Ku70 association and increases caspase 8activation27	increased Ku70 acetylation triggers FLIP polyubiquitination and causes its degradation through the proteasome27	SUMOylation of caspase 8 at K156 alters its nuclear localization but does not interfere in its activation28
ERK1	acetylated ERK1 at K72 enhances the enzymatic activity and affects ATP binding29	PHD domain of E3 ligase MEKK1 acts as an upstream activator of ERK1 and JNK, which promotes their degradation through the proteasomal pathway30	SUMOylation of nNOS at K725 and K739 enhances NO production, which is required for ERK1/2 activity in nNOS-positive neurons31
PARP1	P300/CREB-induced PARP1 acetylation causes coactivation of NF-κβ-dependent transcription32	polyubiquitination of PARP1 at K48 regulates its degradation33	SUMOylation of PARP1 at K486 through SUMO1 and SUMO3 decreases its p300-mediated acetylation, which restrains transcriptional coactivator functions34
AKT1	acetylation of Akt at K163 and K377 increases the neuronal differentiation35	E3 Ligase TRAF6 promotes Ak1 polyubiquitination at K63 and promotes membrane localization and its phosphorylation36	decreases Akt SUMOylation at K276 and K301 and affects Akt-induced Bcl-X alternative splicing37
ERBB2	acetylation of ERBB2 increases its stability38	ubiquitination of ERBB2 through E3 ligase CHIP decreases its stability and facilitates its proteasomal degradation39	SUMOylation of ERBB2 at K23 promotes its transcriptional repression40
DNMT1	DNMT1 is destabilized with Tip60-induced acetylation41	acetylation of DNMT1 triggers ubiquitination with UHRF1 and promotes its proteasomal degradation41	SUMOylation of DNMT1 enhances demethylase activity in vivo and modulates its interaction with HDAC42
MYC	P300-mediated Myc acetylation increases the transcriptional activity and control Myc protein turnover43	USP28-induced Myc ubiquitination promotes its stability and promotes its degradation through interaction with FBW7γ44	K52, K148, K157, and K317 SUMOylation of Myc promotes its degradation regulated by PIAS1 and RNF445
APP	increased H3 and H4 acetylation of APP enhances its transcriptional activity, which increases EGR1 and c-FOS expression46	enhanced ubiquitination of APP decreases its full-length expression and thus decreases Aβ generation47	SUMOylation of APP decreases Aβ production, whereas SENP1 and SENP2 decrease APP SUMOylation48
GAPDH	GAPDH acetylation at K256 increases its activity in glucose response49	S-nitrosylation of B23 at cysteine 275 enhances b23-SIAH1 binding through the decreased E3 ligase activity of SIAH1 and exerts neuroprotective effects50
CDK1	acetylation of CDK1 at K33 requires CDK1: cyclin B binding51	CDK master target of SUMOylation. Inhibition of CDK1 SUMOylation alters its status on CDK1 and its interacting proteins. Decreased CDK1 SUMOylation enhances its activity52	TRAP1 silencing enhances CDK1 ubiquitination, increases MAD2 degradation, and decreases nuclear translocation of the CDK1/cyclin B complex53