Guergnon Julien, Godet Angélique N, Galioot Amandine, Falanga Pierre Barthélémy, Colle Jean-Hervé, Cayla Xavier, Garcia Alphonse
Laboratoire E3 Phosphatases-Unité Signalisation Moléculaire et Activation Cellulaire, Institut Pasteur 25, rue du Dr Roux, 75015 Paris, France.
Biochim Biophys Acta. 2011 Nov;1812(11):1498-507. doi: 10.1016/j.bbadis.2011.07.001. Epub 2011 Aug 10.
Protein phosphatase 2A (PP2A) is a large family of holoenzymes that comprises 1% of total cellular proteins and accounts for the majority of Ser/Thr phosphatase activity in eukaryotic cells. Although initially viewed as constitutive housekeeping enzymes, it is now well established that PP2A proteins represent a family of highly and sophistically regulated phosphatases. The past decade, multiple complementary studies have improved our knowledge about structural and functional regulation of PP2A holoenzymes. In this regard, after summarizing major cellular regulation, this review will mainly focus on discussing a particulate biological strategy, used by various viruses, which is based on the targeting of PP2A enzymes by viral proteins in order to specifically deregulate, for their own benefit, cellular pathways of their hosts. The impact of such PP2A targeting for research in human diseases, and in further therapeutic developments, is also discussed.
蛋白磷酸酶2A(PP2A)是一个庞大的全酶家族,占细胞总蛋白的1%,在真核细胞中占丝氨酸/苏氨酸磷酸酶活性的大部分。尽管最初被视为组成型管家酶,但现在已经明确,PP2A蛋白代表了一类受到高度复杂调控的磷酸酶家族。在过去十年中,多项互补研究增进了我们对PP2A全酶结构和功能调控的了解。在这方面,在总结主要细胞调控之后,本综述将主要聚焦于讨论一种特定的生物学策略,各种病毒采用这种策略,通过病毒蛋白靶向PP2A酶,以便为自身利益而特异性地破坏宿主细胞的信号通路。还讨论了这种PP2A靶向对人类疾病研究及进一步治疗发展的影响。