Inhibition of farnesylation blocks growth but not differentiation in FRTL-5 thyroid cells
| Autor: | Chiara Laezza, Maurizio Bifulco, Salvatore M. Aloj |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
endocrine system
medicine.medical_specialty Protein Prenylation Thyroid Gland Mevalonic Acid Thyrotropin Reductase Biochemistry Cell Line chemistry.chemical_compound Dolichol Prenylation Internal medicine polycyclic compounds medicine Animals Lovastatin biology DNA synthesis Farnesylation Inhibition Cell Differentiation DNA General Medicine Farnesol Rats Endocrinology chemistry HMG-CoA reductase biology.protein Protein farnesylation Cattle Hydroxymethylglutaryl CoA Reductases lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Cell Division medicine.drug |
| Zdroj: | Biochimie. 81:287-290 |
| ISSN: | 0300-9084 |
| DOI: | 10.1016/s0300-9084(99)80072-8 |
| Popis: | The cholesterol lowering drug lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, blocks DNA synthesis and proliferation of thyrotropin (TSH) primed FRTL-5 rat thyroid cells. The blockade can be completely prevented and/or reversed by mevalonate and largely prevented and/or reversed by farnesol whereas cholesterol and/or other non-sterol mevalonate derivatives such as ubiquinone, dolichol or isopentenyladenosine are ineffective. TSH-dependent augmentation of cyclic-AMP and cAMP dependent differentiated functions, such as iodide uptake, are unaffected by lovastatin. 3 H-Thymidine incorporation into DNA is also decreased by α-hydroxyfarnesyl-phosphonic acid, an inhibitor of protein farnesylation which mimicks the effect of lovastatin since it also leaves unaffected TSH stimulated iodide uptake. It is suggested that the HMG-CoA reductase inhibitor lovastatin affects cell proliferation mainly through inhibition of protein farnesylation which results in altered function proteins relevant for proliferation control, notably p21 ras and/or other small GTPases. |
| Databáze: | OpenAIRE |
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