Cancer isoform of a tumor-associated cell surface NADH oxidase (tNOX) has properties of a prion

We have described a drug-responsive form of a cell surface NADH oxidase (hy droquinone oxidase) of cancer cells (tNOX) that exhibits unusual characteri stics including resistance to proteases, resistance to cyanogen bromide dig estion, and an ability to form amyloid filaments closely resembling those o f spongiform encephalopathies and ail of which are characteristics of PrPsc (PrPres), the presumed infective and proteinase K resistant particle of th e scrapie prion. The tNOX protein from the HeLa cell surface copurified wit h authentic,glyceraldehyde-3 phosphate dehydrogenase (muscle form) (GAPDH). Surprisingly, the tNOX-associated muscle GAPDH also was proteinase K resis tant. In this paper, we show that combination of authentic rabbit muscle GA PDH with tNOX renders the GAPDH resistant to proteinase K digestion. This p roperty, that of converting the normal form of a protein into a likeness of itself, is one of the defining characteristics of the group of proteins de signated as prions.