Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers.
Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers.
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DOI：
10.1016/j.gene.2009.01.020
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发表时间：
2009-05-01
期刊：
影响因子：
3.5
通讯作者：
Smith MM
中科院分区：
文献类型：
--
作者：
Iizuka M;Takahashi Y;Mizzen CA;Cook RG;Fujita M;Allis CD;Frierson HF Jr;Fukusato T;Smith MM
除了充分表征的蛋白质，包括前复制复合物，最近的研究表明，染色质结构在DNA复制起始中起着重要的作用。这些染色质因子之一是组蛋白乙酰转移酶（HAT）Hbo 1，其在HAT酶中是独特的，因为其充当DNA复制的正调节剂。然而，Hbo 1的几个基本性质以前没有被研究过，包括其内在的催化活性，其在细胞中的分子丰度，以及其在原发性癌细胞中的表达模式。在这里，我们表明，重组Hbo 1可以乙酰化核小体组蛋白H4在体外，与赖氨酸5和12的偏好。使用半定量的蛋白质印迹分析，我们发现，Hbo 1是大约等摩尔的活跃的复制起点在正常的人成纤维细胞的数量，但一个数量级更丰富的MCF 7和Saos-2建立的癌细胞系。在11个原发性人类肿瘤类型的Hbo 1免疫组化显示强Hbo 1蛋白表达的睾丸癌，卵巢癌，乳腺癌，胃/食管癌，膀胱癌。
In addition to the well-characterized proteins that comprise the pre-replicative complex, recent studies suggest that chromatin structure plays an important role in DNA replication initiation. One of these chromatin factors is the histone acetyltransferase (HAT) Hbo1 which is unique among HAT enzymes in that it serves as a positive regulator of DNA replication. However, several of the basic properties of Hbo1 have not been previously examined, including its intrinsic catalytic activity, its molecular abundance in cells, and its pattern of expression in primary cancer cells. Here we show that recombinant Hbo1 can acetylate nucleosomal histone H4 in vitro, with a preference for lysines 5 and 12. Using semi-quantitative western blot analysis, we find that Hbo1 is approximately equimolar with the number of active replication origins in normal human fibroblasts but is an order of magnitude more abundant in both MCF7 and Saos-2 established cancer cell lines. Immunohistochemistry for Hbo1 in 11 primary human tumor types revealed strong Hbo1 protein expression in carcinomas of the testis, ovary, breast, stomach/esophagus, and bladder.
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