Abstract
Tubulins and microtubules (MTs) represent targets for taxane-based chemotherapy. To date, several lines of evidence suggest that effectiveness of compounds binding tubulin often relies on different post-translational modifications on tubulins. Among them, methylation was recently associated to drug resistance mechanisms impairing taxanes binding. The sea urchin is recognized as a research model in several fields including fertilization, embryo development and toxicology. To date, some α- and β-tubulin genes have been identified in P. lividus, while no data are available in echinoderms for arginine methyl transferases (PRMT). To evaluate the exploiting of the sea urchin embryo in the field of antiproliferative drug development, we carried out a survey of the expressed α- and β-tubulin gene sets, together with a comprehensive analysis of the PRMT gene family and of the methylable arginine residues in P. lividus tubulins. Because of their specificities, the sea urchin embryo may represent an interesting tool for dissecting mechanisms of tubulin targeting drug action. Therefore, results herein reported provide evidences supporting the P. lividus embryo as animal system for testing antiproliferative drugs.
Highlights
It is well known that different α- and β-tubulin isotypes contribute to create an evolutionary conserved network of highly dynamic filaments, with key roles in cellular architecture and physiology [1].The α- and β-tubulin dimers linearly assemble to create polarized proto-filaments with β-tubulin subunits exposed to the solvent at the plus end, while the minus-end is capped by α-tubulin subunits [2,3]
Because of the synchrony in cleavage times related to the correlation between cell cycle regulation and mitotic apparatus of the sea urchin embryo system, tubulins and tubulin targeting drugs may represent an interesting tool for analyse antimitotic molecules that affect tubulin dynamics and drug activity on MT assembly and stability [41]
The availability of large-scale transcriptome collections freely available on public databases allowed us to carry out a transcriptome survey in the sea urchin embryo P. lividus
Summary
It is well known that different α- and β-tubulin isotypes contribute to create an evolutionary conserved network of highly dynamic filaments, with key roles in cellular architecture and physiology [1]. Because of the synchrony in cleavage times related to the correlation between cell cycle regulation and mitotic apparatus of the sea urchin embryo system, tubulins and tubulin targeting drugs may represent an interesting tool for analyse antimitotic molecules that affect tubulin dynamics and drug activity on MT assembly and stability [41]. In the present work, we carried out a survey of the expressed α- and β-tubulin gene sets, together with a comprehensive analysis of the PRMT gene family and the predicted methylable arginine residues in P. lividus tubulins. This will provide the basal elements for a tool kit to study arginine methylation sensitive drugs
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