In this paper we have studied a PDZ protein domain as a possible tool for cellular targeting of the ribosome inactivating protein Saporin, exploiting the ability of PDZ domains to recognize and bind short peptide sequences located at the C-terminus of a cognate protein. We have focused our attention on the PDZ domain from hCASK (Human calcium/calmodulin-dependent serine protein kinase) that binds extracellular CD98 in epithelial cells, being this antigen recognized as a marker for several human tumors and particularly considered a negative prognostic marker for human glioblastoma. We produced recombinant fusions of one or two hCASK-PDZ domains with the ribosome inactivating protein Saporin and assayed them on two human glioblastoma cell lines (GL15 and U87). These constructs proved to be toxic, with increasing activity as a function of the number of PDZ domains, and induce cell death by apoptotic mechanisms in a dose-dependent and/or time dependent manner. J. Cell. Biochem. 116: 1256-1266, 2015.

Giansanti, F., Sabatini, D., Pennacchio, M.R., Scotti, S., Angelucci, F., Dhez, A.C., et al. (2015). PDZ domain in the engineering and production of a saporin chimeric toxin as a tool for targeting cancer cells. JOURNAL OF CELLULAR BIOCHEMISTRY, 116(7), 1256-1266 [10.1002/jcb.25080].

PDZ domain in the engineering and production of a saporin chimeric toxin as a tool for targeting cancer cells

GIORDANO, ANTONIO;
2015-01-01

Abstract

In this paper we have studied a PDZ protein domain as a possible tool for cellular targeting of the ribosome inactivating protein Saporin, exploiting the ability of PDZ domains to recognize and bind short peptide sequences located at the C-terminus of a cognate protein. We have focused our attention on the PDZ domain from hCASK (Human calcium/calmodulin-dependent serine protein kinase) that binds extracellular CD98 in epithelial cells, being this antigen recognized as a marker for several human tumors and particularly considered a negative prognostic marker for human glioblastoma. We produced recombinant fusions of one or two hCASK-PDZ domains with the ribosome inactivating protein Saporin and assayed them on two human glioblastoma cell lines (GL15 and U87). These constructs proved to be toxic, with increasing activity as a function of the number of PDZ domains, and induce cell death by apoptotic mechanisms in a dose-dependent and/or time dependent manner. J. Cell. Biochem. 116: 1256-1266, 2015.
2015
Giansanti, F., Sabatini, D., Pennacchio, M.R., Scotti, S., Angelucci, F., Dhez, A.C., et al. (2015). PDZ domain in the engineering and production of a saporin chimeric toxin as a tool for targeting cancer cells. JOURNAL OF CELLULAR BIOCHEMISTRY, 116(7), 1256-1266 [10.1002/jcb.25080].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/997494
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