Hiroyuki Saito

Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates

Significance Approximately 50 human diseases are associated with deposition of abnormally aggregated proteins that propagate in a prion-like manner. The tumor suppressor p53 forms amyloid-like aggregates; however, how p53 aggregates propagate remains unclear. Here, we identified heparan sulfate (HS), the common and major nonprotein component of in vivo deposits of various protein aggregates, as a mediator of prion-like propagation of p53 aggregates in cultured cells. Our immunohistochemical analysis showing codeposition of p53 and highly sulfated domains of HS in ovarian cancer tissues strongly support the role of HS-mediated propagation of p53 aggregates in cancer pathology. Accordingly, our results provide a mechanism of propagation of p53 aggregates that is mediated by HS. Elucidation of detailed biological relevance in cancer is warranted.