Depletion of uracil-DNA glycosylase activity is associated with decreased cell proliferation.
Uracil-DNA glycosylase (UNG) is the primary enzyme responsible for removing uracil residues from DNA. Increasing evidence suggests that UNG may be a potential target for the development of novel antiviral and/or anticancer agents. To determine whether the uracil-DNA glycosylase inhibitor protein (UGI) could be used to specifically target UNGs intracellularly, we developed a construct that expresses UGI as a fusion protein with the TAT-protein transduction domain and described a novel method for the purification of recombinant TAT-UGI. Treatment of several cell types with TAT-UGI resulted in a dose- and time-dependent decrease in UNG activity. A somewhat surprising effect of TAT-UGI treatment was the decrease in cell proliferation, but not in cell viability. The results of this study support the premise that UNG can be used as a potential therapeutic target and also demonstrate that protein transduction can be used to modulate UNG activity.
Studebaker
A W
AW
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA.
Ariza
M E
ME
Williams
M V
MV
D017209:Apoptosis; D049109:Cell Proliferation; D045647:DNA Glycosylases / Q000172:deficiency* / Q000235:genetics; D004789:Enzyme Activation; D018014:Gene Transfer Techniques; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D051981:Uracil-DNA Glycosidase; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D014764:Viral Proteins; C027619:uracil-DNA glycosylase inhibitor protein, B. subtilis bacteriophage; D045647:DNA Glycosylases; D051981:Uracil-DNA Glycosidase