Biology Department, Brookhaven National Laboratory, 50 Bell Avenue, Building 463, Upton, NY 11973-5000, USA.
Mol Cell Biochem. 2010 Jun;339(1-2):271-84. doi: 10.1007/s11010-010-0390-0. Epub 2010 Feb 11.
Hat1 was the first histone acetyltransferase identified; however, its biological function is still unclear. In this report, it is shown for the first time that human Hat1 has two isoforms. Isoform a has 418 amino acids (aa) and is localized exclusively in the nuclear matrix of normal human keratinocytes (NHKs). Isoform b has 334 aa and is located in the cytoplasm, the nucleoplasm, attached to the chromatin and to the nuclear matrix. Immunohistochemical analyses revealed that the bulk of Hat1 is confined to the nucleus, with much lesser amounts in the cytoplasm. Cells undergoing mitotic division have an elevated amount of Hat1 compared to those that are non-mitotic. Senescent cells, however, exhibit a higher concentration of Hat1 in the cytoplasm compare to proliferating cells and the amount of Hat1 in the nucleus decreases with the progression of senescence. NHKs exposed to hydrogen peroxide (H(2)O(2)) or to a beam of high mass and energy ion particles displayed bright nuclear staining for Hat1, a phenotype that was not observed in NHKs exposed to gamma-rays. We established that the enhanced nuclear staining for Hat1 in response to these treatments is regulated by the PI3K and the mitogen-activated protein kinase signaling pathways. Our observations clearly implicate Hat1 in the cellular response assuring the survival of the treated cells.
Hat1 是第一个被鉴定的组蛋白乙酰转移酶；然而，其生物学功能仍不清楚。在本报告中，首次表明人 Hat1 有两种同工型。同工型 a 有 418 个氨基酸（aa），仅定位于正常人类角质形成细胞（NHK）的核基质中。同工型 b 有 334 个 aa，位于细胞质、核浆中，附着于染色质和核基质上。免疫组织化学分析显示 Hat1 的大部分局限于核内，细胞质内的含量较少。有丝分裂分裂的细胞与非有丝分裂的细胞相比，有更高含量的 Hat1。然而，衰老细胞在细胞质中显示出比增殖细胞更高浓度的 Hat1，并且核内 Hat1 的量随着衰老的进展而减少。暴露于过氧化氢（H 2 O 2 ）或大质量和高能离子束的 NHK 显示出 Hat1 的核染色明亮，而暴露于γ射线的 NHK 则没有观察到这种表型。我们确定，PI3K 和有丝分裂原激活的蛋白激酶信号通路调节了这些处理后 Hat1 的增强核染色。我们的观察结果清楚地表明 Hat1 参与了细胞反应，以确保处理细胞的存活。
