Table 1.
Summary of findings on SUMOylation pathway proteins in HD and polyQ disorders.
| SUMOylation pathway protein | Model | Event | Effect | Ref. |
|---|---|---|---|---|
| PIAS1 | zQ175 KI mice and HD patient-derived iPSCs | KD | DNA damage repair responses and normalized transcriptional profiles | Morozko et al. (2021) |
| R6/2 mice | KD and Overexpression | Reduction of insoluble protein and phenotypic benefit | Ochaba et al. (2016) | |
| Rhes | Striatal neuronal cells (STHdhQ7/Q7) or HD mutants (STHdhQ111/Q111) | Rhes-mediated mHtt transport | Facilitation of cell–cell transport of mHtt | Sharma and Subramaniam (2019) |
| HEK293 cells | Binding to mHtt | mHtt increased disaggregation and cytotoxicity | Subramaniam et al. (2009) | |
| Rhes KO mice | Binding to E1 and Ubc9 | Ubc9 binding to Htt and cross-SUMOylation of E1 and Ubc9 | Subramaniam et al. (2010) | |
| Rhes KO N171-82Q mice | mTORC1 signaling dysregulating | Early striatal motor deficit | Swarnkar et al. (2015) | |
| STUbL Slx5 | Yeast plasmids expressing 25Q and 103Q Htt | Expression and transcriptional properties of aggregation-prone Htt constructs | Reduced toxicity and abnormal transcriptional activity | Ohkuni et al. (2018) |
| SUMO-1 | NIID brain tissue and PC12 cells | Localization into fibrils of tissues and nuclear inclusions | Recruitment of SUMO-1 modified proteins into insoluble nuclear inclusions and proteasomal dysfunction | Pountney et al. (2003) |
| PC12 cells | SUMO-1 and atrophin-1co-transfection | Accelerated aggregate formation and cell death | Terashima et al. (2002) | |
| Brain tissue (HD, DRPLA, SCA1 and MJD) and B05 transgenic mouse | Increased SUMOylated proteins in cerebellar cortex | SUMO-1 activation contributes to polyQ diseases | Ueda et al. (2002) | |
| Brain tissue (MSA) | Cytoplasmic accumulation of α-synuclein, tau or HttQ74-GFP | SUMO-1 colocalization with lysosomes related to glial protein aggregates and protein aggregation | Wong et al. (2013) | |
| SUMO-2 | HeLa cells | Htt SUMO-2 modification | Decreased accumulation | O’Rourke et al. (2013) |
DRPLA: dentatorubral-pallidoluysian atrophy; E1: SUMO activating enzyme E1; GFP: green fluorescent protein; HD: Huntington’s disease; HEK: human embryonic kidney cells; Htt: huntingtin; iPSCs: induced pluripotent stem cells; KD: knockdown; KI: knock-in; KO: knockout; mHtt: mutant huntingtin; MJD: Machado-Joseph disease; MSA: multiple system atrophy; mTORC1: mechanistic target of rapamycin complex 1; NIID: neuronal intranuclear inclusion disease; PolyQ: polyglutamine; PIAS1: Protein Inhibitor of Activated STAT 1; Q: glutamine; Rhes: Ras homolog enriched in the striatum; SCA1: spinocerebellar ataxia type 1; STUbL: SUMO-targeted ubiquitin ligase; Ubc9: SUMO conjugating enzyme 9.