Abstract by Kristina Kohler
Chemistry and Biochemistry
Mechanisms of Upstream TNK1 Regulation Affect Cancer Proliferation and Autophagy
TNK1, a cytosolic tyrosine kinase, promotes cancer proliferation and chemoresistance; it is necessary for the functioning of 14-3-3z, a phospho-binding protein which regulates a variety of pro-survival functions. However, TNK1’s specific role and mechanisms of regulation are unknown. Our lab used confocal microscopy and proteomics-based analyses to characterize TNK1’s interactome, its impact on cell motility and autophagic activity, and its upstream regulation by the tyrosine receptor kinase pDGFR. We propose that pDGFR functions as a molecular switch for activating 14-3-3z-TNK1 binding, resulting in increased cell motility and proliferation. Conversely, when pDGFR is not activated, TNK1 is not phosphorylated and cannot bind to 14-3-3z. Our data suggests that a lack of 14-3-3z-TNK1 binding induces autophagy, a putative mechanism for activating chemoresistance. With a greater understanding of its function and regulation, TNK1 could become a viable therapeutic target for slowing tumor growth and overriding chemoresistance.