Does transduced p27 induce apoptosis in human tumor cell lines?
p27 is a cyclin-dependent kinase inhibitor involved in the negative regulation of G1 progression in response to a number of antiproliferative signals. In this study, we examined the 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 and whether these transduced proteins induced apoptosis in the cells. 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 basic domain of human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) protein possesses the ability to traverse biological membranes efficiently in a process termed protein transduction. Although 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 tremendous potential to deliver large-sized compounds into the cells. Transduction of TAT-fusion proteins affected the proliferation of human tumor cell lines, depending on the type of protein and cell line. By Western blot analysis it was shown that some cell cycle regulatory proteins were affected, and that some proteins were responsible for the induction of apoptosis.
Grdisa
Mira
M
Laboratory of Molecular Oncology, Division of Molecular Medicine, Rudjer Bosković Institute, Bijenicka 54, 10 000 Zagreb, Croatia. grdisa@rudjer.irb.hr
Mikecin
Ana-Matea
AM
Poznic
Miroslav
M
D017209:Apoptosis / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014161:Transduction, Genetic
D018797:Cell Cycle Proteins; D018809:Proliferating Cell Nuclear Antigen; D011993:Recombinant Fusion Proteins; C413374:p27 antigen