Xia Xiaoyu, Gholkar Ankur, Senese Silvia, Torres Jorge Z
a Department of Chemistry and Biochemistry; University of California ; Los Angeles , CA , USA.
Cell Cycle. 2015;14(12):1938-47. doi: 10.1080/15384101.2015.1026487.
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.
亮氨酸羧基甲基转移酶-1（LCMT1）和蛋白质磷酸酶甲酯酶-1（PME-1）是调节蛋白质磷酸酶2A催化亚基（PP2AC）甲基化的关键酶。LCMT1和PME-1与细胞生长和增殖的调节有关，但其潜在机制仍不清楚。我们在此展示了LCMT1-PME-1甲基化平衡在控制有丝分裂纺锤体大小方面的重要作用。LCMT1的缺失或PME-1的过表达导致纺锤体长。相反，PME-1的缺失、PME-1的药物抑制或LCMT1的过表达导致纺锤体短。此外，LCMT1-PME-1甲基化平衡的扰动导致有丝分裂停滞、纺锤体组装检查点激活、细胞分裂缺陷、凋亡诱导和细胞活力降低。因此，我们认为LCMT1-PME-1甲基化平衡对于调节有丝分裂纺锤体大小从而实现正常细胞分裂至关重要。
