engleski

Cancer treatment by TAT-mediated protein transduction into the cells

Transduction is a biochemical technique for the introduction of full-length proteins into the cells. This process occurres in a rapid, concentration dependent fashion that appears to be independent of receptors and transporters. Transduction of peptides and proteins has a broad implications in experimental systems for regulating intracellular processes and has the potential to be use in the development of the new therapeutic strategies for cancer therapy, therapy of infectious diseases, and development of vaccines. TAT protein from HIV-1 virus, which enters into cells in concentration dependent manner, was isolated. TAT-protein is able to cross cell membranes also if it is cross-linked to some other protein, to increase its intracellular concentration. Primary and transformed cells are equally susceptible to TAT-fusion proteins transduction. Protein transduction domain (PTDs) such as that in TAT protein are capable of mediating the transfer of proteins across the plasma membrane into nearly all eukaryotic cells. Poly-arginine (6-12 residue) also has the same transduction activity as the PTDs. PTDs have become widely used as tools for the delivery of proteins into cells in culture, and even into the tissuees of living animals. TAT transduction system has been exploited and refined to address difficult biological questions. Transduction of TAT-p27 fusion protein clarified cell migration of human HepG2 hepatocellular carcinoma cells. A TAT-p16 fusion protein, a specific inhibitor of cyclin-dependent kinase cdk4/cdk6 complexes and prevented hyperphosphorylation of retinoblastoma protein (pRb), elicited a G1-specific cell-cycle arrest. Also was shown that protein transduced dendritic cells may be effective vaccines for the treatment of cancer. In our hands we have been shown that transduced TAT-p27wt, pt-mutated or N'-truncated effected proliferation of cells in culture, depending on concentration and type of the cells. According the results, the different signal transduction pathways were envolved.

cancer; TAT-proteins

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