SUMMARY. Philadelphia chromosome is a result of reciprocal translocation between chromosomes 9 and 22 and serves as a distinct marker of several types of myeloproliferative disorders. Such translocation generates different types of fusions of bcr and abl genes. These fusions differ in presence or absence of certain types of BCR domains and in molecular weight of corresponding chimeric proteins. BCR-ABLp230 is associated with chronic neutrophilic leukemia, BCR-ABLp210 – with chronic myelogenous leukemia, BCR-ABLp190 – with acute lymphoblastic leukemia. Pleckstrin homology domain of BCR is present in p210 and absent in p190 type of fusion protein. Mass-spectromic analysis previously identified 23 potential candidates for interaction with PH domain, including cortactin that is responsible for actin branching. In present work we show that BCR protein colocalized with actin and cortactin at K562 cells periphery. It also formed clusters of colocalization with clathrin and cortactin and was located at points of actin branching, which was shown by STED super-resolution microscopy and regular confocal microscopy of live HEK 293T cells. Live confocal microscopy also identified a relatively large structure in cytoplasm where dynamic comovement of BCR, clathrin and actin occurred. This strongly resembles Golgi complex, as trans-Golgi network is a typical location of clathrin-coated vesicle sorting and assembly. Our findings indicate that BCR in tandem with cortactin may have an important role in dynamic actin-membrane rearrangements that affect clathrin-mediated endocytosis and Golgi vesicular transport. The disruption of its function by abnormal tyrosine kinase activity of ABL may promote cancer phenotype.
Keywords: Bacillus subtilis, riboflavin, mutagenesis, phylogeny, UV radiation, producer strain
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