EXPANDING THE ROLE OF SULFOTYROSINE MODIFICATIONS TO MITOSIS
Document Type
Presentation
Start Date
22-10-2010 8:45 AM
End Date
22-10-2010 9:00 AM
Description
Post-translational modifications are known to determine the activity, localization, interactions, and turnover rate of an ever-expanding list of proteins. These modifications are believed to increase the dynamic nature of the eukaryotic proteome by as much as two to three orders of magnitude. For example, tyrosine sulfation is a post-translational modification that drives essential proteinprotein interactions necessary in several critical biochemical processes. Despite the fact that sulfotyrosine is believed to occur on as much as 1 % of the eukaryotic proteome, only approximately 60 proteins and peptides bearing this modification have been recognized, all of which are extracellular.Using newly available techniques, we discovered sulfotyrosine on a cytosolic protein, the human Eg5 kinesin that is essential for mitosis. Using a published computational algorithm, a lone site of sulfotyrosination was predicted on Eg5 at an allosteric site within its motor domain, and this site is critical for Eg5 sensitivity to putative anticancer drugs. Western blots probed with anti-sulfotyrosine antibody detected at least one site of sulfotyrosine within the motor domain of Eg5 in a human cell line. Based on these results, we predict that the drug binding site on Eg5 is affected by sulfotyrosine and may need to be considered in designing second-generation chemotherapeutics targeted against this enzyme. Second, and more broadly, as sulfotyrosine likely regulates an essential cytoplasmic protein, this opens the door for the possibility that this modification is not limited to extracellular proteins and instead may regulate a wide number of cellular processes.
Recommended Citation
Buckley, Rebecca and Kim, S., "EXPANDING THE ROLE OF SULFOTYROSINE MODIFICATIONS TO MITOSIS" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 2.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/presentation1/2
EXPANDING THE ROLE OF SULFOTYROSINE MODIFICATIONS TO MITOSIS
Post-translational modifications are known to determine the activity, localization, interactions, and turnover rate of an ever-expanding list of proteins. These modifications are believed to increase the dynamic nature of the eukaryotic proteome by as much as two to three orders of magnitude. For example, tyrosine sulfation is a post-translational modification that drives essential proteinprotein interactions necessary in several critical biochemical processes. Despite the fact that sulfotyrosine is believed to occur on as much as 1 % of the eukaryotic proteome, only approximately 60 proteins and peptides bearing this modification have been recognized, all of which are extracellular.Using newly available techniques, we discovered sulfotyrosine on a cytosolic protein, the human Eg5 kinesin that is essential for mitosis. Using a published computational algorithm, a lone site of sulfotyrosination was predicted on Eg5 at an allosteric site within its motor domain, and this site is critical for Eg5 sensitivity to putative anticancer drugs. Western blots probed with anti-sulfotyrosine antibody detected at least one site of sulfotyrosine within the motor domain of Eg5 in a human cell line. Based on these results, we predict that the drug binding site on Eg5 is affected by sulfotyrosine and may need to be considered in designing second-generation chemotherapeutics targeted against this enzyme. Second, and more broadly, as sulfotyrosine likely regulates an essential cytoplasmic protein, this opens the door for the possibility that this modification is not limited to extracellular proteins and instead may regulate a wide number of cellular processes.