Periostin shows increased evolutionary plasticity in its alternatively spliced region.
Periostin shows increased evolutionary plasticity in its alternatively spliced region.
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DOI：
10.1186/1471-2148-10-30
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发表时间：
2010-01-28
影响因子：
3.4
通讯作者：
Andrade-Navarro MA
中科院分区：
文献类型：
--
作者：
Hoersch S;Andrade-Navarro MA
Periostin(POSTN)是一种功能不明的分泌型细胞外基质蛋白，与骨骼和心脏发育以及癌症有关。在人类和小鼠中，已知它在其C末端区域经历了选择性剪接，该区域缺乏已知的蛋白质结构域。Periostin的差异表达，有时是特定的剪接异构体，在广泛的人类癌症中观察到，包括乳腺癌、胰腺癌和结肠癌。在这里，我们结合脊椎动物的基因组和转录序列数据来研究Periostin的进化，特别是它的C-末端区域。我们发现，在脊椎动物中，Periostin的C-末端部分在外显子数量、长度和剪接模式方面明显比Periostin的其余部分更不同，我们将其解释为Periostin与其邻近的转化生长因子β诱导的(TGFBI)分裂后新的功能化的结果。我们还定义了Periostin的连续13个氨基酸重复单位-在硬骨鱼中很好地保守，但在高等脊椎动物中更鲜为人知-其二级结构被预测为连续的β链。我们认为，这些β链可能通过延长的β-拉链介导与其他蛋白质的结合作用，其方式类似于已报道的细菌细胞壁蛋白中的重复单元与人纤维连接蛋白结合的方式。我们的结果是在越来越多的完整脊椎动物基因组的帮助下获得的，证明了Periostin C-末端区域的进化可塑性，并首次为其功能作用提供了基础。
Periostin (POSTN) is a secreted extracellular matrix protein of poorly defined function that has been related to bone and heart development as well as to cancer. In human and mouse, it is known to undergo alternative splicing in its C-terminal region, which is devoid of known protein domains. Differential expression of periostin, sometimes of specific splicing isoforms, is observed in a broad range of human cancers, including breast, pancreatic, and colon cancer. Here, we combine genomic and transcriptomic sequence data from vertebrate organisms to study the evolution of periostin and particularly of its C-terminal region. We found that the C-terminal part of periostin is markedly more variable among vertebrates than the rest of periostin in terms of exon count, length, and splicing pattern, which we interpret as a consequence of neofunctionalization after the split between periostin and its paralog transforming growth factor, beta-induced (TGFBI). We also defined periostin's sequential 13-amino acid repeat units - well conserved in teleost fish, but more obscure in higher vertebrates - whose secondary structure is predicted to be consecutive beta strands. We suggest that these beta strands may mediate binding interactions with other proteins through an extended beta-zipper in a manner similar to the way repeat units in bacterial cell wall proteins have been reported to bind human fibronectin. Our results, obtained with the help of the increasingly large collection of complete vertebrate genomes, document the evolutionary plasticity of periostin's C-terminal region, and for the first time suggest a basis for its functional role.
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影响因子：
7
作者：
Castronovo, Vincent;Waltregny, David;Neri, Dario
通讯作者：
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影响因子：
4.5
作者：
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DOI：
10.1161/01.atv.9.1.21
发表时间：
1989-01-01
期刊：
ARTERIOSCLEROSIS
影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
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