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- W2782346085 abstract "27 The COMPARE algorithm provides an instrumental platform for correlating drug sensitivities and/or molecular targets among the 60 human cancer cell lines of the National Cancer Institute (NCI-60). In this study, the level of tubulin acetylation in the NCI-60 cell lines is examined by quantitative western blotting and used as a seed for COMPARE analysis against the gene expression database generated from microarray data. This analysis generates a list of genes that correlate with tubulin acetylation. One such gene with a strong negative correlation is farnesyltransferase (FTase), such that cell lines with high levels of tubulin acetylation have low FTase gene expression. We have also examined the protein levels of FTase in all 60 cell lines, which confirm the negative correlation between FTase and tubulin acetylation. In addition, western blotting and immunofluorescence studies reveal that inhibition of FTase activity in cancer cells dramatically enhances the level of tubulin acetylation. Interestingly, co-immunoprecipitation experiments demonstrate that FTase interacts with the tubulin deacetylase HDAC6, providing evidence that these two enzymes are biologically linked. Lastly, we show that FTase inhibitors suppress HDAC6 activity in a cell-free tubulin deacetylation assay. These data indicate a pharmacological interplay between FTase and HDAC6. Additional mechanistic studies investigating the molecular nature of FTase interaction with HDAC6 are currently under investigation in our laboratory." @default.
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- W2782346085 date "2005-05-01" @default.
- W2782346085 modified "2023-09-24" @default.
- W2782346085 title "COMPARE analysis of the NCI-60 cancer cell lines reveals a pharmacological interplay between farnesyltransferase and tubulin deacetylase." @default.
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