Spatial control of protein phosphatase 2A (de)methylation
Spatial control of protein phosphatase 2A (de)methylation
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DOI：
10.1016/j.yexcr.2007.07.030
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发表时间：
2008-01-01
影响因子：
3.7
通讯作者：
Janssens, Veerle
中科院分区：
文献类型：
--
作者：
Longin, Sari;Zwaenepoel, Karen;Janssens, Veerle
蛋白磷酸酶2A催化亚基可逆甲基化(PP2A(C)(1))是一种重要的调控机制，在调控B亚基的选择性募集中起着至关重要的作用。在这里，我们研究了亮氨酸羧甲基转移酶(LCMT1)和蛋白磷酸酶甲酯酶(PME-1)这两种催化这一过程的酶的亚细胞定位。结果表明，PME-1主要定位于细胞核，具有功能性的核定位信号，而LCMT1在细胞核中表达较少，主要定位于细胞质、高尔基体和晚期内小体。甲基化敏感的抗PP2A(C)抗体的间接免疫荧光显示与PP2A(C)的甲基化状态有很好的相关性，去甲基化的PP2A(C)基本上是核的。在整个有丝分裂过程中，去甲基化的PP2A(C)与有丝分裂纺锤体有关，在细胞质分裂过程中与卵裂沟有关。过度表达。PME-1的过度表达而不是非活性突变体的PP2A(C)在细胞核中的去甲基化增加，而缺乏NLS的细胞质PME-1突变体的过表达导致细胞质中的去甲基化增加-然而，在所有情况下，都没有任何明显的功能后果。无论其酯酶活性或定位如何，PME-1都与不活跃的PP2A群体相关。我们认为，稳定这个不活跃的核PP2A池是PME-1在体内的主要功能。(C)2007 Elsevier Inc.保留所有权利。
Reversible methylation of the protein phosphatase 2A catalytic subunit (PP2A(C)(1)) 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(C) antibodies revealed a good correlation with the methylation status of PP2A(C), demethylated PP2A(C) being substantially nuclear. Throughout mitosis, demethylated PP2A(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(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. (C) 2007 Elsevier Inc. All rights reserved.