A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size |
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| Authors: | Xiaoyu Xia Ankur Gholkar Silvia Senese Jorge Z Torres |
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| Institution: | 1.Department of Chemistry and Biochemistry; University of California; Los Angeles, CA, USA;2.Jonsson Comprehensive Cancer Center; University of California; Los Angeles, CA, USA;3.Molecular Biology Institute; University of California; Los Angeles, CA, USA |
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| Abstract: | Leucine carboxyl methyltransferase-1 (LCMT1) and protein phosphatase methylesterase-1 (PME-1) are essential enzymes that regulate the methylation of the protein phosphatase 2A catalytic subunit (PP2AC). LCMT1 and PME-1 have been linked to the regulation of cell growth and proliferation, but the underlying mechanisms have remained elusive. We show here an important role for an LCMT1-PME-1 methylation equilibrium in controlling mitotic spindle size. Depletion of LCMT1 or overexpression of PME-1 led to long spindles. In contrast, depletion of PME-1, pharmacological inhibition of PME-1 or overexpression of LCMT1 led to short spindles. Furthermore, perturbation of the LCMT1-PME-1 methylation equilibrium led to mitotic arrest, spindle assembly checkpoint activation, defective cell divisions, induction of apoptosis and reduced cell viability. Thus, we propose that the LCMT1-PME-1 methylation equilibrium is critical for regulating mitotic spindle size and thereby proper cell division. |
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| Keywords: | cell division LCMT1 methylation mitotic spindle PME-1 |
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