Spatial control of protein phosphatase 2A (de)methylation
- Protein Phosphorylation and Proteomics Laboratory, Department of Molecular Cell Biology, Faculty of Medicine, KU Leuven, Herestraat 49 bus 901, B-3000 Leuven (Belgium)
Reversible methylation of the protein phosphatase 2A catalytic subunit (PP2A{sub C}) is an important regulatory mechanism playing a crucial role in the selective recruitment of regulatory B subunits. Here, we investigated the subcellular localization of leucine carboxyl methyltransferase (LCMT1) and protein phosphatase methylesterase (PME-1), the two enzymes catalyzing this process. The results show that PME-1 is predominantly localized in the nucleus and harbors a functional nuclear localization signal, whereas LCMT1 is underrepresented in the nucleus and mainly localizes to the cytoplasm, Golgi region and late endosomes. Indirect immunofluorescence with methylation-sensitive anti-PP2A{sub C} antibodies revealed a good correlation with the methylation status of PP2A{sub C}, demethylated PP2A{sub C} being substantially nuclear. Throughout mitosis, demethylated PP2A{sub C} is associated with the mitotic spindle and during cytokinesis with the cleavage furrow. Overexpression of PME-1, but not of an inactive mutant, results in increased demethylation of PP2A{sub C} in the nucleus, whereas overexpression of a cytoplasmic PME-1 mutant lacking the NLS results in increased demethylation in the cytoplasm-in all cases, however, without any obvious functional consequences. PME-1 associates with an inactive PP2A population, regardless of its esterase activity or localization. We propose that stabilization of this inactive, nuclear PP2A pool is a major in vivo function of PME-1.
- OSTI ID:
- 21045918
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 314; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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