Doctoral defence 11.10.2024: Vignesh Srinivasan
Doctoral defence on Friday 11.10.2024 at 12:00 – 14:00
Haartman Institute, Hall 1, Haartmaninkatu 3
Vignesh Srinivasan, from the Neuronal Signaling group at the Minerva Institute, will defend his dissertation on October 11, 2024, on the novel roles of the protein deubiquitinase USP14 in proteostasis regulation and cell stress responses.
Protein quality control is an important process to ensure accurate levels and functions of different proteins in the cell. Ubiquitin specific protease-14 (USP14) is a deubiquitinating enzyme that serves essential functions in regulating cell degradation pathways and also ER stress.
In this thesis work, Vignesh Srinivasan has studied the specific roles of USP14) in the regulation of proteasome and autophagy pathway using different cell models including neuronal cells and thyroid tumor cells. Employing mutations of USP14 as well gene deletion of USP14 by the CRISPR/Cas method followed substitution of the protein in cells, Vignesh Srinivasan could then detect novel cellular pathways influenced by USP14. Furthermore, a proteomic analysis revealed that USP14 can undergo post-transcriptional modifications including phosphorylation of specific serine residues that affects its functions.
Disturbances in protein degradation occur in many human diseases characterized by accumulation of misfolded or mutant proteins, such as metabolic diseases, neurodegenerative disorders, and several cancer types. There are two main pathways for protein degradation in the cell, the ubiquitin proteasome system (UPS) and the autophagy-lysosome pathway, and both of these pathways are potential targets for intervention in diseases. The results in this thesis show that USP14 can function both in the regulation of UPS and in autophagy as well as in organelle homeostasis in the cell.
The work can set the stage for further studies on the functional significance of in USP14 in different biological pathways and disease conditions that in the long-run may pave the way for novel therapies.