Abstract

Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease characterized by the occurrence of the Bcr-Abl fusion oncoprotein, which resulted from a reciprocal translocation between chromosomes 9 and 22. The Golgi complex-localized protein 1(GLG1) was identified by mass spectrometry as a potential interaction partner to the pleckstrin homology (PH) domain of the Bcr-Abl oncoprotein. The GLG1 protein is a transmembrane protein known also as MG-160, ESL-1, and CFR-1. Irregularities in the GLG1 functions affect the adhesion, mobility, and migration of cells. In this study, the interaction between the GLG1 protein and the Bcr-Abl oncoprotein is shown for the first time. With imunofluorescence and confocal microscopy, colocalization of the GLG1protein and the Bcr-Abl oncoprotein to the Golgi complex has been detected. A GLG1 protein form phosphorylated at the tyrosine site in K562 cells has also been detected, and Tyr phosphorylation sites for GLG1 isoforms were predicted. The authors believe that the oncoprotein phosphorylates the GLG1 protein, at the cost of its Abl part, during the GLG1–Bcr-Abl protein interaction in the Golgi complex, thus affecting its activity and disrupting the descending signaling pathways that may be crucial for the development and progression of the disease.

中文翻译：

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Bcl-Abl癌蛋白与Glg1蛋白在K562细胞中的相互作用：其在慢性粒细胞白血病发病机理中的作用

摘要

慢性粒细胞白血病（CML）是一种克隆性骨髓增生性疾病，其特征是Bcr-Abl融合癌蛋白的发生，其是由9号和22号染色体之间的相互易位引起的。通过质谱法鉴定了高尔基复合体定位蛋白1（GLG1）。作为Bcr-Abl癌蛋白的pleckstrin同源（PH）域的潜在相互作用伴侣。GLG1蛋白是一种跨膜蛋白，也称为MG-160，ESL-1和CFR-1。GLG1功能的不规则性会影响细胞的粘附，迁移和迁移。在这项研究中，首次显示了GLG1蛋白与Bcr-Abl癌蛋白之间的相互作用。通过免疫荧光和共聚焦显微镜，已检测到GLG1蛋白和Bcr-Abl癌蛋白在高尔基体中的共定位。还检测到了在K562细胞中酪氨酸位点磷酸化的GLG1蛋白形式，并预测了GLG1亚型的Tyr磷酸化位点。作者认为，癌蛋白在高尔基体中的GLG1-Bcr-Abl蛋白相互作用过程中，以Abl部分为代价使GLG1蛋白磷酸化，从而影响其活性并破坏可能对发育至关重要的下行信号通路。和疾病的进展。