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TAT-Mediated Delivery of p27 in Tumor Cell Lines as a Potential Therapeutic Peptide - Pages 78-86

Ana-Matea Mikecin and Mira Grdisa

Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb, Croatia




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    Abstract: TAT-fusion proteins (TAT-wt-p27, TAT-pt-p27, TAT-N'-p27) were introduced into the cells by protein transduction method. The mechanism by which transduced 27 influences on the regulation of cell cycle and apoptosis, were explored.

    TAT-p27-fusion proteins affected the proliferation of examined cell lines depending on type of the cells and protein. Transduced p27 induced accumulation of cyclin D1 and D3, with slight differences among the form of protein. Expression of cyclin D2 and E was mainly unchanged. Furthermore, TAT fusion proteins promoted apoptosis, which resulted in activation of caspase 3, appearance of poly (ADP-ribose) polymerase and DNA fragments, as well as the activation of apoptosis-inducing factor.

    The results pointed that transduced p27 activates apoptosis through activation of different signal transduction pathways. Thus, the molecule of p27 could be appropriate for treatment of tumors with deregulated its function. Also, the protein transduction method could find the application in specifically targeted cancer therapy.

    Keywords: Apoptosis, cell cycle, p27, TAT fusion proteins.


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