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Parnian, Matthew

University of British Columbia

PTEN is a critical tumor suppressor that regulates cell growth and survival by counteracting the PI3K/AKT signaling pathway. Genetic mutations in PTEN are implicated in various cancers and neurodevelopmental disorders, yet the precise impact of these mutations on PTEN’s protein interactions remains poorly understood. This study employs proximity labeling proteomics and affinity purification-mass spectrometry (AP-MS) to unravel the mechanisms underlying PTEN variant-associated pathophysiology. Using BioID labeling and protein mass spectrometry, I elucidate the impact of different PTEN variants on proximity-labled protein partners, revealing significant variations in labeling intensities across different missense variants. These differences suggest that certain variants disrupt PTEN’s protein interactions, potentially contributing to functional impairments. Among the interactors, PTPN13 was identified as a candidate interacting partner, offering insights into PTEN’s role in phosphatase-mediated signaling. However, precise quantification of this interaction remains challenging. By elucidating the impact of PTEN mutations on its interactome, this study advances our understanding of the molecular consequences of PTEN dysfunction in disease. These results lay the foundation for future investigations into PTEN-related signaling pathways, with potential implications for targeted therapeutic strategies. Further biochemical and structural studies will be required to validate these interactions and assess their relevance in pathological conditions.

Text

2025-04-22

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/90715

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/