Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 phosphorylation on Thr187 and accumulates p27Kip1 in the nucleus: implications for breast cancer therapy.

@article{Kazi2009BlockadeOP,
  title={Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 phosphorylation on Thr187 and accumulates p27Kip1 in the nucleus: implications for breast cancer therapy.},
  author={Aslamuzzaman Kazi and Adam Carie and Michelle A. Blaskovich and Cynthia J Bucher and Van Thai and Stacy Moulder and Hairuo Peng and Dora Carrico and Erin E Pusateri and Warren Jack Pledger and Norbert Berndt and Andrew D. Hamilton and Sa{\"i}d M. Sebti},
  journal={Molecular and cellular biology},
  year={2009},
  volume={29 8},
  pages={2254-63}
}
We describe the design of a potent and selective peptidomimetic inhibitor of geranylgeranyltransferase I (GGTI), GGTI-2418, and its methyl ester GGTI-2417, which increases the levels of the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) and induces breast tumor regression in vivo. Experiments with p27(Kip1) small interfering RNA in breast cancer cells and p27(Kip1) null murine embryonic fibroblasts demonstrate that the ability of GGTI-2417 to induce cell death requires p27(Kip1). GGTI-2417… CONTINUE READING