The neuronal microtubule-associated protein tau is a substrate for caspase-3 and an effector of apoptosis.
We have identified a class of tau fragments inducing apoptosis in different cellular contexts, including a human teratocarcinoma-derived cell line (NT2 cells) representing committed human neuronal precursors. We have found a transition point inside the tau molecule beyond which the fragments lose their ability to induce apoptosis. This transition point is located around one of the putative caspase-3 cleavage sites. This is the only site that can be effectively used by caspase-3 in vitro, releasing the C-terminal 19 amino acids of tau. These results establish tau as a substrate for an apoptotic protease that turns tau itself into an effector of apoptosis. Accordingly, tau may be involved in a self-propagating process like what has been predicted for the pathogenesis of different neurodegenerative disorders.
Fasulo
L
L
Neuroscience Programme and INFM Unit, International School for Advanced Studies, Trieste, Italy.
Ugolini
G
G
Visintin
M
M
Bradbury
A
A
Brancolini
C
C
Verzillo
V
V
Novak
M
M
Cattaneo
A
A
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D018243:Teratocarcinoma; D014162:Transfection; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D010446:Peptide Fragments; D011994:Recombinant Proteins; D016875:tau Proteins; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases