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.