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Exploring the Role of Intrinsically Disordered Regions in TNK1-Mediated Signaling and Phase Separation

Semester: Summer 2024


Presentation description

Thirty-eight negative kinase 1 (TNK1) is a poorly understood non-receptor tyrosine kinase. Although our group's recent paper describes its mechanism of activation and its role in carcinogenesis, its biological function and mechanism of regulation still need to be elucidated. TNK1 activation is regulated by the 14-3-3 protein, which binds to TNK1 when TNK1 is phosphorylated within its disordered proline-rich region (PRR), specifically at the serine 502 (S502). Our data suggest that 14-3-3 keeps TNK1 inactive by preventing it from undergoing liquid-liquid phase separation (LLPS), a mechanism utilized by several proteins for spatiotemporal regulation in biochemical signalling. My project focuses on understanding how intrinsic disorder within the PRR of TNK1 contributes to TNK1 phase separation and kinase activity. Intrinsically disordered regions (IDRs) are protein sequences that lack a fixed three-dimensional structure under physiological conditions. IDRs are characterized by their flexibility and ability to engage in multiple interactions, often acting as hubs for protein-protein interactions. We hypothesize that intrinsic disorder is sufficient to drive TNK1 phase separation and further activation; therefore, to test this hypothesis we deleted the PRR and generated versions of TNK1 in which the PRR is replaced by IDRs from the proteins Tau, TDP43, and A2B1, which are known to undergo LLPS. I will measure the requirement and possible sufficiency of intrinsic disorder for TNK1 activity by assessing the ability of TNK1 WT and PRR mutants to phosphorylate substrates, including STAT1. These results will provide insight into the role of intrinsic disorder in the regulation of cancer-related kinases, that can be proposed as new therapeutic targets.

Presenter Name: Peace Taiwo
Presentation Type: Poster
Presentation Format: In Person
Presentation #47
College: Medicine
School / Department: Oncological Sciences
Research Mentor: Josh Andersen
Time: 9:00 AM
Physical Location or Zoom link:

Ballroom