Blockade of Protein Geranylgeranylation Inhibits Cdk2-Dependent p27^Kip1 Phosphorylation on Thr187 and Accumulates p27^Kip1 in the Nucleus: Implications for Breast Cancer Therapy

Abstract excerpt

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...

Topics

Share this publication in a Topic to start or enrich a Post.

• Share to Cancer-related Molecular Pathways
• Share to DNA Repair Mechanisms
• Share to RNA Research and Splicing