Colocalization of USP1 and РН domain of Bcr-Abl oncoprotein in terms of chronic myeloid leukemia cell rearrangements

Аннотация

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.