Antonenko S V, Gurianov D S, Тelegeev G D
Tsitol Genet. 2016 Jul-Aug;50(4):11-5.
The development of chronic myeloid leukemia (CML) is the result of a reciprocal translocation between chromosomes 9 and 22 due to the emergence of Philadelphia chromosome. The product of this mutation is a hybrid oncoprotein Bcr-Abl. According to the results of mass spectrometric analysis, USP1 protein was identified as a potential candidate for interaction with the PH domain Bcr-Abl oncoprotein. Due to the deubiquitination properties, USP1 protein can prevent proteasomal degradation of Bcr-Abl oncoprotein in a cell and, consequently, contribute to its accumulation, and the progression of the disease. In this work, creating the genetic constructs, we detected the USP1 protein localization in the cell. Also, a nuclear colocalization of USP1 protein with PH domain of Bcr-Abl oncoprotein in HEK293T cells was shown. The results are important for understanding the implications of the Philadelphia chromosome emergence, and the development of new methods for CML treatment, since the recent techniques are not always effective due to the emergence of numerous mutations that cause drug resistance and relapse of the disease.
慢性髓性白血病（CML）的发生是由于费城染色体的出现导致9号和22号染色体之间发生相互易位的结果。这种突变的产物是一种融合癌蛋白Bcr-Abl。根据质谱分析结果，USP1蛋白被鉴定为与PH结构域Bcr-Abl癌蛋白相互作用的潜在候选蛋白。由于具有去泛素化特性，USP1蛋白可防止细胞中Bcr-Abl癌蛋白的蛋白酶体降解，从而促进其积累以及疾病的进展。在这项工作中，通过构建基因载体，我们检测了USP1蛋白在细胞中的定位。此外，还显示了在HEK293T细胞中USP1蛋白与Bcr-Abl癌蛋白的PH结构域在细胞核中共定位。这些结果对于理解费城染色体出现的影响以及开发CML治疗新方法具有重要意义，因为由于导致耐药性和疾病复发的众多突变的出现，目前的技术并不总是有效。
