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PP2A调节亚基B56基因家族的进化分析

Evolutionary Analysis of the B56 Gene Family of PP2A Regulatory Subunits.

作者信息

Sommer Lauren M, Cho Hyuk, Choudhary Madhusudan, Seeling Joni M

机构信息

Department of Biological Sciences, Sam Houston State University, Huntsville, TX 77341, USA.

Department of Computer Science, Sam Houston State University, Huntsville, TX 77341, USA.

出版信息

Int J Mol Sci. 2015 May 5;16(5):10134-57. doi: 10.3390/ijms160510134.

DOI:10.3390/ijms160510134
PMID:25950761
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4463637/
Abstract

Protein phosphatase 2A (PP2A) is an abundant serine/threonine phosphatase that functions as a tumor suppressor in numerous cell-cell signaling pathways, including Wnt, myc, and ras. The B56 subunit of PP2A regulates its activity, and is encoded by five genes in humans. B56 proteins share a central core domain, but have divergent amino- and carboxy-termini, which are thought to provide isoform specificity. We performed phylogenetic analyses to better understand the evolution of the B56 gene family. We found that B56 was present as a single gene in eukaryotes prior to the divergence of animals, fungi, protists, and plants, and that B56 gene duplication prior to the divergence of protostomes and deuterostomes led to the origin of two B56 subfamilies, B56αβε and B56γδ. Further duplications led to three B56αβε genes and two B56γδ in vertebrates. Several nonvertebrate B56 gene names are based on distinct vertebrate isoform names, and would best be renamed. B56 subfamily genes lack significant divergence within primitive chordates, but each became distinct in complex vertebrates. Two vertebrate lineages have undergone B56 gene loss, Xenopus and Aves. In Xenopus, B56δ function may be compensated for by an alternatively spliced transcript, B56δ/γ, encoding a B56δ-like amino-terminal region and a B56γ core.

摘要

蛋白磷酸酶2A(PP2A)是一种丰富的丝氨酸/苏氨酸磷酸酶,在众多细胞间信号通路(包括Wnt、myc和ras信号通路)中发挥肿瘤抑制作用。PP2A的B56亚基调节其活性,在人类中由五个基因编码。B56蛋白共享一个中央核心结构域,但具有不同的氨基末端和羧基末端,这些末端被认为提供了同工型特异性。我们进行了系统发育分析,以更好地了解B56基因家族的进化。我们发现,在动物、真菌、原生生物和植物分化之前,B56在真核生物中作为单个基因存在,并且在原口动物和后口动物分化之前的B56基因复制导致了两个B56亚家族B56αβε和B56γδ的起源。进一步的复制导致脊椎动物中有三个B56αβε基因和两个B56γδ基因。几个非脊椎动物B56基因名称基于不同的脊椎动物同工型名称,最好重新命名它们。B56亚家族基因在原始脊索动物中缺乏显著差异,但在复杂的脊椎动物中各自变得不同。有两个脊椎动物谱系经历了B56基因丢失,即非洲爪蟾和鸟类。在非洲爪蟾中,B56δ的功能可能由一个选择性剪接的转录本B56δ/γ补偿,该转录本编码一个类似B56δ的氨基末端区域和一个B56γ核心。

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