Insulin-Degrading-Enzyme (IDE) is a Zn2+-dependent peptidase highly conserved throughout evolution and ubiquitously distributed in mammalian tissues wherein it displays a prevalent cytosolic localization. We have recently demonstrated a novel Heat Shock Protein-like behaviour of IDE and its association with the 26S proteasome. In the present study, we examine the mechanistic and molecular features of IDE-26S proteasome interaction in a cell experimental model, extending the investigation also to the effect of IDE on the enzymatic activities of the 26S proteasome. Further, kinetic investigations indicate that the 26S proteasome activity undergoes a functional modulation by IDE through an extra-catalytic mechanism. The IDE-26S proteasome interaction was analyzed during the Heat Shock Response and we report novel findings on IDE intracellular distribution that might be of critical relevance for cell metabolism.

Sbardella, D., Tundo, G., Sciandra, F., Bozzi, M., Gioia, M., Ciaccio, C., Tarantino, U., Brancaccio, A., Coletta, M., Marini, S., Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution, <<PLOS ONE>>, 2015; 10 (7): e0132455-e0132455. [doi:10.1371/journal.pone.0132455] [http://hdl.handle.net/10807/72455]

Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution

Bozzi, Manuela;
2015

Abstract

Insulin-Degrading-Enzyme (IDE) is a Zn2+-dependent peptidase highly conserved throughout evolution and ubiquitously distributed in mammalian tissues wherein it displays a prevalent cytosolic localization. We have recently demonstrated a novel Heat Shock Protein-like behaviour of IDE and its association with the 26S proteasome. In the present study, we examine the mechanistic and molecular features of IDE-26S proteasome interaction in a cell experimental model, extending the investigation also to the effect of IDE on the enzymatic activities of the 26S proteasome. Further, kinetic investigations indicate that the 26S proteasome activity undergoes a functional modulation by IDE through an extra-catalytic mechanism. The IDE-26S proteasome interaction was analyzed during the Heat Shock Response and we report novel findings on IDE intracellular distribution that might be of critical relevance for cell metabolism.
Inglese
Sbardella, D., Tundo, G., Sciandra, F., Bozzi, M., Gioia, M., Ciaccio, C., Tarantino, U., Brancaccio, A., Coletta, M., Marini, S., Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution, <<PLOS ONE>>, 2015; 10 (7): e0132455-e0132455. [doi:10.1371/journal.pone.0132455] [http://hdl.handle.net/10807/72455]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/72455
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