Abstract by Kristina Kohler
Tsz Yin Chan
Chemistry and Biochemistry
TNK1 reveals a novel autoinhibitory function of the UBA domain
TNK1 is a little-studied cytosolic kinase that promotes cancer proliferation and growth. Despite its oncogenic role in various cancer types, the mechanisms which regulate TNK1 are poorly understood. Our previous research has shown that a C-terminus truncation mutant of TNK1 has upregulated activity. We propose that the C-terminus of TNK1 contains a unique ubiquitin-association (UBA) domain that functions as an auto-inhibitory domain. Using predictive protein modeling and western blot analyses, we found that ubiquitin-TNK1 binding disrupts the kinase activity of TNK1. We further discovered that the UBA hinders TNK1 self-oligomerization. Together, our data suggest a novel mechanism of UBA-mediated kinase regulation in cancer.