蛋白磷酸酶2A（PP2A）通过多种细胞周期蛋白依赖性激酶（CDK）平衡视网膜母细胞瘤蛋白（pRB）和有丝分裂蛋白的磷酸化：PP2A功能紊乱在癌症中的潜在影响
PP2A Counterbalances Phosphorylation of pRB and Mitotic Proteins by Multiple CDKs: Potential Implications for PP2A Disruption in Cancer.
作者信息
Kurimchak Alison, Graña Xavier
机构信息
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, USA.
出版信息
Genes Cancer. 2012 Nov;3(11-12):739-48. doi: 10.1177/1947601912473479.
Abstract
Protein Phosphatase 2A (PP2A) consists of a collection of heterotrimeric serine/threonine phosphatase holoenzymes that play multiple roles in cell signaling via dephosphorylation of numerous substrates of a large family of serine/threonine kinases. PP2A substrate specificity is mediated by B regulatory subunits of four different families, which selectively recognize diverse substrates by mechanisms that are not well understood. Among the many signaling pathways with critical PP2A functions are several deregulated in cancer cells, and PP2A is a know tumor suppressor. However, the precise composition of the heterotrimeric PP2A complexes with tumor supressor activity is not well understood. This review is centered on the emerging role of the B regulatory subunit B55α and related subfamilly members in the modulation of the phosphorylation state of pocket proteins and mitotic CDK substrates, as well as the implications of PP2A function disruption in cancer in the context of these activities.
摘要
蛋白磷酸酶2A（PP2A）由一组异源三聚体丝氨酸/苏氨酸磷酸酶全酶组成，这些全酶通过使一大类丝氨酸/苏氨酸激酶的众多底物去磷酸化，在细胞信号传导中发挥多种作用。PP2A的底物特异性由四个不同家族的B调节亚基介导，这些亚基通过尚未完全了解的机制选择性识别不同的底物。在具有关键PP2A功能的众多信号通路中，有几条在癌细胞中失调，并且PP2A是一种已知的肿瘤抑制因子。然而，具有肿瘤抑制活性的异源三聚体PP2A复合物的确切组成尚未完全了解。本综述聚焦于B调节亚基B55α及相关亚家族成员在调节口袋蛋白和有丝分裂CDK底物磷酸化状态方面的新作用，以及在这些活动背景下PP2A功能破坏在癌症中的影响。
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