Visit our Expo - Redox and Inflammation signaling 2012

Session XVII : Cell signaling in health and disease Poster XVII, 19
TAT fusion proteins as a drug delivery system
Mira Grdi)a, Ana-Matea Mikecin and Miroslav Pozni',
Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb,
Croatia Email: grdisa@irb.hr
TAT protein, a basic domain of human immunodeficiency virus type 1 (HIV-1), possess the
ability to traverse biological membranes efficiently in a process termed «protein
transduction». Protein transduction can be described as the direct uptake by the cell of
exogenous proteins/peptides, as a result of a specific property of the protein/peptide
component. The mechanism is unknown. Transduction occurs in receptor-transporter-
independent manner that appears to target the lipid bilayer directly. Thus, HIV-1 Tat proteins
have tramendous potential to deliver large-sized compounds (drugs) into the cells.
In the rpesent study, transduction of full-length Tat-p27, pt-mutated Tat-p27 and N'- Tat-p27
(truncated p27 on the C-terminal end) fusion proteins into human tumor cell lines was
examined and whether these transduced proteins induced apoptosis in the cells.
The proteins (p27, p23, Mp27) were transdused into different cell lines (NALM, MOLT, Raji,
SuDHL, K562, RKO and MiaPaCa2) and their effect on proliferation of the cells were
measured. The fusion proteins influenced moderately on the proliferation of different cell
lines and varied among the proteins and type of the cells. A transduced p27 did not
remarkable influence on proliferation of examined cell lines. Mutated p27 inhibited the
proliferation of examined cell lines up to 30 %. On the other hand, a transduction of p23
protein, truncated form of p27, inhibited the proliferation all of examined cell lines 30-60 %.
Also the effects on expression of host p27 protein were examined, as well as an influence on
induction of apoptosis.
The expression of cell cycle regulatory proteins (cycD2, D3, cycE) were not remarkable
affected with transduced proteins. It seems that transduced proteins induced apoptosis in
examined cell lines. According the results, different apoptotic pathways were induced,
depending on the type of cells.
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