Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Transport Systems / chemistry*
-
Amino Acid Transport Systems / pharmacology*
-
Antineoplastic Agents, Phytogenic / pharmacology
-
Apoptosis / drug effects*
-
Biological Assay
-
CDC2-CDC28 Kinases / pharmacology*
-
Carrier Proteins / chemistry*
-
Carrier Proteins / pharmacology*
-
Cell Cycle / drug effects*
-
Cell Division
-
Cell Membrane
-
Cyclin-Dependent Kinase 2
-
DNA / biosynthesis
-
HeLa Cells
-
Humans
-
Paclitaxel / pharmacology
-
Peptide Fragments / pharmacokinetics
-
Peptide Fragments / pharmacology*
-
Permeability
-
Saccharomyces cerevisiae Proteins / chemistry*
-
Saccharomyces cerevisiae Proteins / pharmacology*
-
Vesicular Transport Proteins
Substances
-
Amino Acid Transport Systems
-
Antineoplastic Agents, Phytogenic
-
Carrier Proteins
-
PEP8 protein, S cerevisiae
-
Peptide Fragments
-
Saccharomyces cerevisiae Proteins
-
TAT2 protein, S cerevisiae
-
Vesicular Transport Proteins
-
DNA
-
CDC2-CDC28 Kinases
-
CDK2 protein, human
-
Cyclin-Dependent Kinase 2
-
Paclitaxel