h-Goliath, paralog of GRAIL, is a new E3 ligase protein, expressed in human leukocytes
h-Goliath, paralog of GRAIL, is a new E3 ligase protein, expressed in human leukocytes
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DOI：
10.1016/j.gene.2006.01.028
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发表时间：
2006-06-07
期刊：
影响因子：
3.5
通讯作者：
Bulle, Frederique
中科院分区：
文献类型：
--
作者：
Guais, Adeline;Siegrist, Sylvie;Bulle, Frederique
在果蝇中，RING指蛋白d-Goliath最初被鉴定为参与胚胎中胚层形成的转录因子[Bouchard，M.L.，Cote，S.，1993.黑腹果蝇发育基因g1编码一种变异的锌指基序蛋白。Gene 125，205 - 209]。在小鼠中，m-Goliath mRNA水平显示在生长因子撤除诱导的骨髓细胞凋亡中增加[Baker，S.J.，Reddy，E.P.，2000.果蝇g1相关新基因--小鼠G1RP的克隆Gene 248，33 - 40]。由于其假定的转录因子在细胞凋亡中的功能，我们克隆了人的cDNA的h-歌利亚和其特征在于在血液和骨髓细胞中的蛋白质的表达。人类蛋白质419 aa（44 kDa），包含一个蛋白酶相关结构域，一个跨膜结构域和一个RING-H2基序。该结构将h-Goliath分类为以GRAIL（与淋巴细胞中的无反应性相关的基因）为创始者的泛素连接酶的人类家族的新成员。这种E3连接酶通过泛素化控制T细胞克隆无反应性的发展[Anandasabapathy，N.，福特，G.S.，Bloom，D.，Holness，C.，Paragas，V，血清学，C.，Skrenta，H.，Hollenhorst，M.，Fathman，C.G.，斯卡尔斯湖，2003. GRAIL：抑制细胞因子基因转录的E3泛素连接酶，在无反应性CD4 + T细胞中表达。免疫力18，535 - 547]。体外泛素化研究支持h-Goliath的E3泛素连接酶活性。在人类中，该蛋白以3种同种型表达，一种主要的同种型在28 kDa，另外两种在46和55 kDa。这些蛋白质来自一个共同的前体（44 kDa），我们观察到使用体外转录-翻译。对健康或白血病样本的血液或骨髓涂片使用免疫组织化学，我们发现蛋白质表达仅限于祖细胞和完全分化的白细胞群体的细胞质。我们在白血病中没有观察到h-Goliath表达或定位的任何修饰。在这些细胞中，这种新的E3泛素连接酶蛋白似乎与细胞的分化状态或细胞凋亡无关。(c)2006 Elsevier B.V.保留所有权利。
In Drosophila, the RING finger protein d-Goliath was originally identified as a transcription factor involved in the embryo mesoderm formation [Bouchard, M.L., Cote, S., 1993. The Drosophila melanogaster developmental gene g1 encodes a variant zinc-finger-motif protein. Gene 125, 205-209]. In mouse, the m-Goliath mRNA level was shown to be increased in growth factor withdrawal-induced apoptosis of myeloid cells [Baker, S.J., Reddy, E.P., 2000. Cloning of murine G1RP, a novel gene related to Drosophila melanogaster g1. Gene 248, 33-40]. Due to its putative function of transcription factor in apoptosis, we cloned the human cDNA for h-Goliath and characterized the expression of the protein in blood and bone marrow cells. The human protein of 419 aa (44 kDa) contains a protease-associated domain, a transmembrane domain and a RING-H2 motif. This structure classifies h-Goliath as a new member of a human family of ubiquitin ligases with GRAIL (gene related to anergy in lymphocytes) as founder. This E3 ligase controls the development of T cell clonal anergy by ubiquitination [Anandasabapathy, N., Ford, G.S., Bloom, D., Holness, C., Paragas, V, Seroogy, C., Skrenta, H., Hollenhorst, M., Fathman, C.G., Scares, L., 2003. GRAIL: an E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4+ T cells. Immunity 18, 535-547]. In vitro ubiquitination studies support the E3 ubiquitin ligase activity of h-Goliath. In human, the protein is expressed under 3 isoforms, a major one at 28 kDa and two others at 46 and 55 kDa. These proteins come from a common precursor (44 kDa) as we observed using in vitro transcription-translation. Using immumohistochemistry on blood or bone marrow smears, of healthy or leukemia samples, we found that the protein expression was restricted to the cytoplasm of progenitors and fully differentiated leukocyte populations. We did not observe any modification of h-Goliath expression or localization in leukemia. In these cells, this new E3 ubiquitin ligase protein does not seem associated with a differentiation state of the cell or with apoptosis. (c) 2006 Elsevier B.V. All rights reserved.