Abstract by Tsz Yin Chan
Tsz Yin Chan
Chemistry and Biochemistry
A novel 14-3-3ζ-dependent mechanism of TNK1 regulation that promote cancer tumorigenesis
The oncogenic phospho-binding protein 14-3-3ζ acts as a scaffolding protein to promote cell growth, survival, and motility. We recently discovered an interaction between 14-3-3ζ and the non-receptor tyrosine kinase TNK1. Although TNK1 has been identified as an oncogenic kinase in multiple genome-wide screens, little is known about its regulation and function. In our study, we identify a cluster of three phosphorylations on TNK1 that promote 14-3-3ζ binding and hence boost TNK1 kinase activity to promote migration of cancer cells. In addition, we discover that the removal of TNK1 C-terminal UBA domain renders TNK1 as a highly active kinase. Finally, we identify mutations in primary human tumors that produce a truncated TNK1 that lacks the UBA domain but possesses constitutive kinase activity. Our current work is focused on understanding the contribution of these mutations to tumorigenesis.