Roles of the intramolecular regions of FE65 in its trans-accumulation and in p53 stabilization in the nuclear matrix of osmotically stressed cells

Abstract

The neural adaptor protein FE65 interacts with the amyloid β-protein precursor (APP). In osmotically stressed cells, the membrane APP-tethered FE65 is released into the cytoplasm and translocates to the nuclear matrix, where it stabilizes p53 via a non-canonical pathway. In this study, we found that the second phosphotyrosine interaction domain (PI2) of FE65 mediated its trans-accumulation in the nuclear matrix of osmotically stressed cells. The carboxyl-terminal half of FE65, which contains the PI2 domain, failed to stabilize p53, suggesting that the amino-terminal half of the protein plays an important role in the stabilization of p53 in osmotically stressed cells. © 2009 Federation of European Biochemical Societies.