P21-dependent G 1 arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228
2000
Effects of FR901228 on Cell Cycle Arrest
publication
Author Information
Author(s): Sandor V, Senderowicz A, Mertins S, Sackett D, Sausville E, Blagosklonny M V, Bates S E
Primary Institution: Medicine Branch, DSC, NCI, NIH, Bethesda, MD, 20892
Hypothesis
Does the histone deacetylase inhibitor FR901228 induce cell cycle arrest through specific mechanisms?
Conclusion
FR901228 causes G1 arrest by downregulating cyclin D1 and upregulating cyclin E, independent of p53.
Supporting Evidence
- FR901228 causes G1 arrest with Rb hypophosphorylation.
- Cyclin D1 protein disappears after treatment with FR901228.
- Cyclin E is upregulated following FR901228 treatment.
- FR901228 induces p21WAF1/CIP1 in a p53-independent manner.
- Cell clones lacking p21 are not arrested in G1 phase.
Takeaway
A new drug called FR901228 can stop cancer cells from growing by changing some proteins in the cells.
Methodology
In vitro kinase assays and analysis of protein levels after treatment with FR901228.
Digital Object Identifier (DOI)
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