Theses and Dissertations

Advisor

Collins, Galen

Committee Member

Rai, Aswathy

Committee Member

Krishnan, Natraj

Date of Degree

5-15-2026

Original embargo terms

Visible MSU Only 1 year

Document Type

Graduate Thesis - Campus Access Only

Major

Agricultural Life Sciences (Biochemistry)

Degree Name

Master of Science (M.S.)

College

College of Agriculture and Life Sciences

Department

Department of Biochemistry, Nutrition and Health Promotion

Abstract

Proteasomes are multi-subunit protein complexes that degrade misfolded or unnecessary proteins to maintain cellular homeostasis. While the cGAS–cGAMP–STING pathway is best known for inducing transcriptional immune responses, its role in directly regulating proteasome function remains unclear. In this study, we investigated whether the second messenger cGAMP modulates 26S proteasome activity in human cells. Proteasome activity was assessed using fluorogenic peptide assays and activity-based labeling following cGAMP treatment. We found that cGAMP rapidly enhances 26S proteasome activity, with the strongest response observed in RPE-1 cells. Dose–response experiments revealed a nonlinear, biphasic pattern of proteasome activation, suggesting an optimal range of cGAMP signaling. This increase occurred without changes in proteasome abundance or assembly and was not blocked by protein synthesis inhibition, indicating activation of pre-existing proteasomes. Pharmacological inhibition of STING attenuated cGAMP-induced proteasome activation. Together, these findings reveal an unrecognized link between cGAS–STING signaling and cellular proteostasis.

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