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Effects of Stathmin N-Terminal Domain Mutations on Cell Cycle, Microtubules Assembly and Dynamics in HeLa Cells

Journal: International Journal of Medicine and Pharmaceutical Sciences (IJMPS) (Vol.4, No. 3)

Publication Date:

Authors : ; ; ;

Page : 91-106

Keywords : Cell Cycle; HeLa; Microtubule; N-Terminal; Stathmin;

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Abstract

Microtubules are major constituents of the cytoskeleton and are involved in many cellular processes such as the formation of the mitotic spindle and intracellular trafficking. These tubular structures, composed by tubulin α/β heterodimers assemble and disassemble with a finely regulated dynamics. Stathmin is a cytosolic phosphoprotein that sequesters tubulin in a non polymerizable complex consisting of two tubulin heterodimers per stathmin molecule (T2S complex). The I19L (IQVKELEKRASGQAFELIL) peptide derived from the stathmin N-terminal domain corresponds to region folded into a "β-hairpin" structure observed in the T2S crystals. To increase the efficiency of this interaction, different mutations were introduced at the level of the I19L peptide and tested in vitro. The results showed that the peptideI19L-K4R-A10R is the most effective to inhibit microtubules assembly. In this work, we introduce these mutations to analyzing their efficiencies on microtubules disassembly and their impact on microtubules dynamic and cell cycle in cancer cell cultures like HeLa. Over expression experiments of wild-type and stathmin mutant containing the double mutation (K9R-A15R similar to the mutations K4R-A10R for the I19L peptide), suggests that this mutant which is less phosphorylated on serine 16 induces microtubules bundles formation, reduces microtubule dynamics and inhibits cell proliferation. We thus suggest that we can ameliorate the binding and efficiency of the N-terminal stathmin part by including this double mutation. This variation has an impact in vitro and in some cellular aspects such as cell proliferation and microtubules dynamics. These findings may lead to a targeted therapy for this type of cancer.

Last modified: 2014-07-16 19:56:32