The Use of GFP-RAS Mutants for The Stimulation of The Statins Mediated Effect on Ras Oncogenes Trafficking in Th Cancer Cells
The statins (HMG-CoA reductase inhibitors) are widely used in medical practice for treatment of hypercholesterolemia due to their ability to inhibit de novo cholesterol synthesis, namely mevalonate pathway. However, statins inhibitory action on HMG-CoA reductase results also in the depletion of intermediate biosynthetic products that post-translationally modify many proteins including Ras. In particular, K, N and H-Ras proteins play an important role in cell proliferation and differentiation. Influence of statins on the proper post-translational modification of Ras proteins could therefore offer the explanation of the cancero-protective effects attributed to statins in recent years. For the possible application of statins in medical practice in role of chemoadjuvants, it is necessary to know the effect of improper posttranslational modifications of Ras proteins on intracellular transport, and hence their involvement in various signalling pathways.
Keywords - Ras, Farnesylation, Palmitoylation, Golgi Aparatus, Endoplasmic Reticulum