Inhibition of USP1, a new partner of Bcr-Abl, results in decrease of Bcr-Abl level in K562 cells
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-2.14533Keywords:
Bcr-Abl oncoprotein, chronic myeloid leukemia, K562 cells, ML323 inhibitor, USP1 proteinAbstract
Summary. Aim: To analyze interaction of ubiquitin specific peptidase 1 (USP1) with Bcr-Abl and to assess the relation between USP1 functional activity and Bcr-Abl expression in K562 chronic myeloid leukemia cells. Materials and Methods: The interaction between USP1 and Bcr-Abl in K562 cells was analyzed by co-immunoprecipitation, Western blot analysis, and confocal microscopy. Results: A direct interaction between Bcr-Abl oncoprotein and USP1 protein in K562 cells was established by co-immunoprecipitation. Immunofluorescence analysis and confocal microscopy revealed that Bcr-Abl/USP1 protein complex is formed in the cell nucleus. The inhibition of USP1 protein activity by ML323 reduced the level of Bcr-Abl oncoprotein in K562 cells. Conclusions: USP1 protein has been identified as a new protein partner of Bcr-Abl oncoprotein in chronic myeloid leukemia. The relationship between the functional activity of USP1 protein and the level of Bcr-Abl oncoprotein has been demonstrated, suggesting that the targeted inhibition of USP1 activity could be a challenging approach for reducing Bcr-Abl expression.
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