title: A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size.
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.
authors.affiliation: a Department of Chemistry and Biochemistry; University of California ; Los Angeles , CA , USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xia
authors.forename: Ankur
authors.initials: A
authors.lastname: Gholkar
authors.forename: Silvia
authors.initials: S
authors.lastname: Senese
authors.forename: Jorge Z
authors.initials: JZ
authors.lastname: Torres
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D017209:Apoptosis; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division; D002470:Cell Survival; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011497:Protein O-Methyltransferase / Q000737:chemistry / Q000235:genetics; D000071636:Protein Phosphatase 2C; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; C524761:LCMT1 protein, human; D011497:Protein O-Methyltransferase; D002265:Carboxylic Ester Hydrolases; C119357:protein phosphatase methylesterase-1; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: LCMT1; PME-1; cell division; methylation; mitotic spindle
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