NR ATHT
AU Say,Y.H.; Hooper,N.M.
TI Functional Characterisation of the N-terminal Fragments Resulting from Two Different Proteolytic Cleavages of the Prion Protein, PrP
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-25
PT Konferenz-Poster
AB Prion diseases, such as Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle are due to aberrant folding of the prion protein, PrP. Its unstructured N-terminus contains octapeptide repeats that bind copper and other metal ions, subsequently having protective effects against metal-induced toxicity and oxidative stress. PrP undergoes alpha- and beta- post-translational cleavages at around residues 110 and 90, respectively, producing functionally elusive N- and C-terminal fragments. The trafficking of the post-cleavage fragments also remains elusive. The present study investigates the role and trafficking of the post-cleavage N-terminal fragments. N1, deltaN1, N2 and deltaN2 constructs (delta indicates deleted signal sequence; targeted directly into the cytosol) as produced in alpha-cleavage and beta-cleavage respectively, were synthesised and stably transfected into human neuroblastoma, SH-SY5Y cells. The N1 and deltaN1 constructs were toxic to the cells, while the stably-expressed N2 and deltaN2 constructs were biochemically characterised by Western Blotting and subcellular fractionation. The effects of the constructs on cell viability and oxidative stress are currently being studied. This study will help to shed some light on the significance of the two different proteolytic processing pathways of PrP.
AD Mr Yee-How Say, Prof. Nigel M. Hooper, University of Leeds, UK
SP englisch
PO Deutschland