Abstract by Madison Frey

Personal Infomation

Presenter's Name

Madison Frey

Degree Level



Tsz-Yin Chan
Chrissy Egbert
Logan Larsen
Kristina Kohler
Julia Maxson
David Huang
Jeffrey Tyner

Abstract Infomation


Chemistry and Biochemistry

Faculty Advisor

Joshua Andersen


14-3-3 Binding Controls TNK1-Driven Oncogenic Signaling


Thirty-eight-Negative-Kinase 1 (TNK1) is a poorly characterized member of the ACK family of Non-receptor tyrosine kinases. TNK1 has been identified in genetic screens as a mediator of tumor cell survival, however, its function and mechanisms of regulation are unknown. Here we identify the first mechanism that controls the activation of TNK1. Through immunoprecipitation and mass spectrometry, we discovered the phospho-binding protein 14-3-3 as a TNK1-interacting protein. We identified a cluster of phosphorylation near the TNK1 C-terminus that mediates its interaction with 14-3-3. Mutation of these sites disrupts TNK1-14-3-3 binding and leads to hyperactivation in TNK1 kinase activity. Mutant 14-3-3 binding of TNK1 potently drives growth factor-independent proliferation of murine B cells invitro and in vivo with kinetics similar to BCR-ABL. In conclusion, inhibition of 14-3-3-TNK1 binding allows TNK1 to become active and drive oncogenic signaling