Introduction: The development of chronic myeloid leukemia (CML) is due to the appearance of the oncoprotein Bcr-Abl. Modern therapy for CML involves the use of Bcr-Abl tyrosine kinase inhibitors, but almost a third of patients develop resistance to these drugs. Therefore, there is an urgent need to develop new approaches for the selective reduction of Bcr-Abl cancer. Malignant cells have mechanisms to suppress the degradation of cancer proteins, the main role in this process is played by deubiquitination enzymes. We believe that Bcr-Abl avoids cellular proteolysis due to USP1 deubiquitinase, which leads to the accumulation of cancer protein and disease progression.

Aim: To study the effect of USP1 deubiquitinase on the level of Bcr-Abl oncoprotein in CML cells.

Materials and methods: K562 cells obtained from a patient with CML at the stage of blast crisis were used in the work. The Bcr-Abl/USP1 protein complex and the effect of deubiquitinase on oncoprotein levels were studied by Western blot and immunofluorescence analysis. Inhibition of USP1 activity was performed using compound ML323. The analysis of the results was performed by quantitative and statistical analysis.

Results: The interaction of deubiquitinase USP1 and Bcr-Abl in K562 cells was detected. The nuclear localization of the USP1 protein and its colocalization with Bcr-Abl in K562 cells were established. It has been shown that under the influence of the ML323 inhibitor, the protein changes its nuclear localization to cytoplasmic, which may be the cause of disruption of the USP1/UAF1 protein complex. It was found that inhibition of deubiquitin activity of USP1 by ML323 is accompanied by a decrease in the level of cancer protein by 65-67% compared with control and loss of colocalization for USP1/BcrAbl proteins.

Conclusions: It was found that the oncoprotein forms a nuclear protein complex with USP1 in CML cells. We believe that USP1 deubiquitinizes Bcr-Abl and thus disrupts its proteosomal degradation, promotes the accumulation of cancer protein and disease progression. The shown effect of USP1 deubiquitinase on the level of Bcr-Abl oncoprotein makes it a promising therapeutic target in the treatment of CML.