PEP8-TAT2, a membrane-permeable peptide, inhibits cyclin-Cdk2 activity in HeLa cells.
Here we show that the PEP8-TAT2 peptide is effectively transduced into HeLa cells and that it inhibits cellular cyclin-Cdk2 activity. Like the PEP8 peptide, the PEP8-TAT2 peptide inhibits Cdk2 activity in vitro with an IC50 value of 5 nM, as determined by an immuno-complex kinase assay. It also inhibits DNA synthesis in and proliferation of cultured HeLa cells by arresting cell cycle at the G1/S transition. Further, the PEP8-TAT2 peptide inhibits cell death-associated Cdk2 activity and thereby prevents apoptotic progression in paclitaxel-treated cells. We propose that this inhibitor peptide is an effective agent to suppress the proliferation of human cancer cells, as well as apoptotic progression, by blocking cellular cyclin-dependent Cdk kinase activity.
Division of Pharmaceutical Biosciences, College of Pharmacy, Seoul National University, 151-742, South Korea.
Kwang-Hoon
KH
Chun
Dae-Kwon
DK
Kim
Yun-Won
YW
Nam
Seung-Ki
SK
Lee
D026905:Amino Acid Transport Systems / Q000737:chemistry* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001681:Biological Assay; D042846:CDC2-CDC28 Kinases / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division; D002462:Cell Membrane; D051357:Cyclin-Dependent Kinase 2; D004247:DNA / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology*; D010539:Permeability; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000494:pharmacology*; D033921:Vesicular Transport Proteins
D026905:Amino Acid Transport Systems; D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; C089990:PEP8 protein, S cerevisiae; D010446:Peptide Fragments; D029701:Saccharomyces cerevisiae Proteins; C429825:TAT2 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D004247:DNA; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D017239:Paclitaxel