SENP1
Faculty Mentor Information
Dr. Dinesh Kumar Verma, Boise State University; and Dr. Yonghwan Kim, Boise State University
Presentation Date
7-15-2026
Abstract
SUMOylation is a reversible posttranslational modification in which a small ubiquitin-like modifier (SUMO) protein is covalently attached to lysine residues on target proteins, typically within a consensus motif (ψ–K–X–E). This dynamic process, regulated by SUMO-conjugating enzymes (E1, E2, E3) and deSUMOylating proteases (SENPs), modulates protein localization, stability, and function. Parkinson’s disease (PD), the second most common progressive neurodegenerative disorder, affects nearly one million individuals in the United States and remains incurable. A key pathological hallmark of PD is the aggregation of α‑synuclein, which drives neuronal degeneration and inflammation. SUMOylation has been reported to increase α‑synuclein solubility, suggesting a potential regulatory role in PD pathology. To investigate this mechanism, rat dopaminergic N27P cells were treated with α‑synuclein pre‑formed fibrils (PFFs) to model PD‑like conditions. After 24 hours, SENP1 expression was markedly elevated, indicating enhanced deSUMOylation activity. To assess SENP1’s role, cells were treated with Momordin Ic, a known SENP1 inhibitor. Proteomic and RNA analyses identified three candidate targets—SSU72, PRKACB, and PSMC5—associated with transcriptional regulation, signaling, and protein degradation. These findings indicate that SENP1‑mediated deSUMOylation modulates key cellular pathways involved in PD progression and may reveal novel therapeutic target.
SENP1
SUMOylation is a reversible posttranslational modification in which a small ubiquitin-like modifier (SUMO) protein is covalently attached to lysine residues on target proteins, typically within a consensus motif (ψ–K–X–E). This dynamic process, regulated by SUMO-conjugating enzymes (E1, E2, E3) and deSUMOylating proteases (SENPs), modulates protein localization, stability, and function. Parkinson’s disease (PD), the second most common progressive neurodegenerative disorder, affects nearly one million individuals in the United States and remains incurable. A key pathological hallmark of PD is the aggregation of α‑synuclein, which drives neuronal degeneration and inflammation. SUMOylation has been reported to increase α‑synuclein solubility, suggesting a potential regulatory role in PD pathology. To investigate this mechanism, rat dopaminergic N27P cells were treated with α‑synuclein pre‑formed fibrils (PFFs) to model PD‑like conditions. After 24 hours, SENP1 expression was markedly elevated, indicating enhanced deSUMOylation activity. To assess SENP1’s role, cells were treated with Momordin Ic, a known SENP1 inhibitor. Proteomic and RNA analyses identified three candidate targets—SSU72, PRKACB, and PSMC5—associated with transcriptional regulation, signaling, and protein degradation. These findings indicate that SENP1‑mediated deSUMOylation modulates key cellular pathways involved in PD progression and may reveal novel therapeutic target.