Proposed Model. Murine pancreatic cancer causes Ikaros degradation and alters T Cell Homeostasis.

<p>We propose a potential molecular mechanism of Ikaros regulation by which under normal conditions, the balance (represented by the solid, black bar) in the concerted action of PP1 and CK2 stabilizes Ikaros protein expression. This results in maintenance of effector CD4/CD8⁺ and regulatory T cell percentages. However, in a pancreatic cancer microenvironment, our findings suggest that there is a decrease in PP1 but an increase in CK2 activity (represented by broken arrow), which leads to ubiquitin-mediated protein degradation of Ikaros. This loss of Ikaros expression results in a loss of T cell homeostasis marked by a reduction of effector CD4/CD8⁺ T cell percentages and an increase of regulatory T cells. Ikaros may therefore be important for regulating T cell immune responses in pancreatic cancer.