Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 278, Issue 44, Pages 43586-43594Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M307194200
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA 89406] Funding Source: Medline
Ask authors/readers for more resources
Mevastatin arrested HCT116 colon cancer cells at the G(1)/S transition and increased cellular levels of p21(CIP1/WAF1). p21-deficient colon cancer cells continued to proliferate in the presence of mevastatin. Although p21 was necessary for the G(1)/S block, the G(1) cyclin-dependent kinases (Cdks) cyclin E-Cdk2 and cyclin D-Cdk4 remained active. Despite the activity of the G(1) Cdks the retinoblastoma protein was hypophosphorylated due to unknown mechanisms that were dependent on the p21 protein. The resulting decrease in cyclin A mRNA and protein led to a decrease in the activity of cyclin A-Cdk2. Therefore, although p21 was required for the G(1)/S arrest of HCT116 colon cancer cells by mevastatin, its mode of action was more complicated than the simple formation of a physical complex with cyclin-Cdk2. This mechanism of inhibition is different from that seen in prostate cancer cells (Ukomadu, C., and Dutta, A. (2003) J. Biol. Chem. 278, 4840-4846) where the activating phosphorylation of cyclin E-Cdk2 is suppressed and p21 is not required, suggesting the existence of cell line-specific differences in the mechanism by which statins arrest the cell cycle.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available