Anti-apoptotic function of EAT/mcl-1 on diseases

早期人类胚胎发生由细胞分化事件的良好调控序列记录，并且同样与通过细胞凋亡调控去除不必要的细胞相关。通过使用胚胎癌（EC）细胞系建立了早期人胚胎发育模型。NCR-G3细胞来源于人睾丸混合EC，具有向神经元、肌源性、上皮细胞和滋养外胚层细胞分化的能力，线粒体是细胞凋亡早期调控的重要细胞器。Bcl-2相关蛋白主要定位于线粒体外膜并调节线粒体通透性。这些重要的功能被认为是启动凋亡机制。编码bcl-2相关蛋白的EAT/mcl-1（EAT）最初是作为在NCR-G3细胞分化早期诱导表达的基因分离的。后来发现，它能抑制细胞凋亡， ...更多信息 在各种诱发骨质疏松的条件下。发现人EAT基因在序列上与bcl-2家族的成员mcl-1相同，mcl-1是在TPA诱导分化成单核细胞/巨噬细胞谱系期间从人髓性白血病细胞系中分离的。EAT基因的鼠直向同源物也已被分离，并已被确定为在鼠胚胎干（ES）细胞和鼠EC细胞系如TT 2、PCC 3和F9中被RA类似地诱导。EAT也已知是立即早期基因，其在其3'非翻译区中具有立即反应盒，如其它立即早期基因如c-fos、c-jun和集落刺激因子-1。这一证据暗示EAT在与胚胎发生相关的细胞分化中的作用。然而，EC分化过程中的精确表达模式和细胞内定位尚未阐明。我们研制了EAT特异性单克隆抗体，并测定了EAT在人EC细胞系中的定位。此外，我们还测定了bcl-2相关蛋白在分化或凋亡的EC细胞和人胚胎发生中的表达。少

Early human embryogenesis is chronicled by a well-regulated sequence of cell differentiation events and is likewise correlated with regulated removal of unnecessary cells by apoptosis. A model of early human embryonic development has been established by the use of embryonal carcinoma (EC) cell lines. NCR-G3 cells were established from a human testicular mixed EC and are able to differentiate into neuronal, myogenic, epithelial as well as the trophectodermal lineage.The mitochondria is an important organelle regulating the early stages of the apoptotic pathway. Bcl-2 related proteins have been shown to localize mainly in the outer mitochondrial membrane and to modulate mitochondrial permeability. These important functions are believed to initiate the apoptotic mechanism. EAT/mcl-1 (EAT), which encodes a bcl-2 related protein, was originally isolated as a gene whose expression is induced at an early stage of differentiation in NCR-G3 cells. It has since been found to inhibit apoptosis un … More der a variety of apoptosis-inducing conditions. The human EAT gene was found to be identical in sequence with mcl-1, a member of the bcl-2 family, which was isolated from a human myeloid leukemia cell line during TPA-induced differentiation into the monocyte/macroahage lineage. The murine orthologue of the EAT gene has also been isolated and has been established to be similarly induced by RA in murine embryonic stem (ES) cells and murine EC cell lines such as TT2, PCC3 and F9. Therefore, EAT functions to enhance cell survival.EAT is also known to be an immediate early gene that has an immediate response box in its 3' untranslated region like other immediate early genes such as c-fos, c-jun and colony stimulation factor-1. This evidence implicates a role for EAT in the cellular differentiation associated with embryogenesis. However, the precise expression pattern and intracellular localization during EC differentiation have not been elucidated. We developed the monoclonal antibody which reacts specifically to EAT and determined the localization of EAT in a human EC cell line. Furthermore, we determined the expression of bcl-2 related proteins in EC cells undergoing differentiation or apoptosis and human embryogenesis. Less