Physiologic functions of PP2A: Lessons from genetically modified mice

被引:101
作者
Reynhout, Sara
Janssens, Veerle
机构
[1] Katholieke Univ Leuven, Dept Cellular & Mol Med, Lab Prot Phosphorylat & Prote, Leuven, Belgium
[2] Leuven Canc Inst LKI, Leuven, Belgium
[3] LBI, Leuven, Belgium
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2019年 / 1866卷 / 01期
关键词
Protein Phosphatase 2A (PP2A); Genetically modified mouse models; Tumor suppressor; Lipid and glucose metabolism; Hematopoiesis and immune system dysfunction; Cardiac dysfunction; Tauopathy; PROTEIN PHOSPHATASE 2A; REGULATORY SUBUNIT; CATALYTIC SUBUNIT; DEVELOPMENTAL REGULATION; HARDERIAN-GLAND; BLOOD-PRESSURE; BETA-CATENIN; CORE ENZYME; LUNG-CANCER; MOUSE MODEL;
D O I
10.1016/j.bbamcr.2018.07.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein Phosphatase 2A (PP2A) encompasses a large family of Ser/Thr phosphatases, consisting of a catalytic C subunit and a structural A subunit that are, in most cases, further bound to a regulatory B-type subunit. The B-type subunits determine function and regulation of PP2A trimers, but despite their importance in PP2A biology, their roles in controlling dephosphorylation of a given substrate in a given cell or tissue remain poorly defined, particularly in the context of a complete organism. Besides twenty PP2A subunit encoding genes, some of which are tissue-specifically expressed, five additional genes encode major regulators of active PP2A trimer assembly, and at least seven genes encode cellular PP2A inhibitors, further adding to the complexity of the mammalian PP2A system. In this review, we summarize current knowledge on physiologic functions of PP2A in germ cell maturation, embryonic development, metabolic regulation, tumor suppression, and homeostasis of adult brain, heart, liver, immune system, lung, intestine, kidney, skin, bone and eye, all retrieved from in vivo studies using PP2A transgenic, knockout or knockin mice. Data from 63 mouse models, generated between 1998 and now, reveal the essentiality of PP2A in vivo, and shed light on tissue-specific functions of particular PP2A subunits on the one hand, and functional redundancies on the other hand. In future, it remains of utmost importance to further characterize the existing models, as well as to generate novel models, with the aim of deepening our insights in PP2A (patho)physiology and, particularly, in the therapeutic potential of PP2A targeting in human disease.
引用
收藏
页码:31 / 50
页数:20
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