∆NP63α AND YB1: A FUNCTIONAL INTERACTION CONTROLLING CELL PROLIFERATION AND MOTILITY

TP63, a member of the p53 gene family, can be expressed as six different protein isoforms. ∆Np63α is the predominantly expressed p63 isoform in squamous epithelia and is restricted to cells with proliferative potential while it is downregulated in cells undergoing terminal differentiation. ∆Np63α plays a critical role in the morphogenesis of organs/tissues developing by epithelial-mesenchimal interactions such as the epidermis, teeth, hair and glands. Herein, we present evidences that the Y box-binding protein-1 (YB-1), a member of the cold shock domain superfamily of proteins, interacts with ∆Np63α but not with the smaller ∆Np63γ isoform. YB-1 is a transcriptional/translational factor involved in cell proliferation, migration and transformation but the molecular mechanisms governing the involvement of YB-1 in these processes are still unclear.YB-1 shuttles between the nucleus and cytoplasm playing different and even conflicting functions according to its sub-cellular localization. We present data showing that enforced expression of ∆Np63α induces YB-1 nuclear localization and accumulation. In the nuclear compartment ∆Np63α and YB-1 activates the expression of the catalytic subunit of the PI3K kinase (PI3KCA) thereby inducing Akt1 phosphorylation and activation of a pro-survival pathway. Furthermore, our data suggest a role for ∆Np63α in the control of cell motility and adhesion through interaction with YB-1. We also present data showing that ∆Np63α and YB1 colocalize in proliferative cells of epithelia. Our data implicate the existence of a ∆Np63α-dependent mechanism governing cell proliferation and migration through the physical association between ∆Np63α and YB-1, a newly isolated p63 molecular partner