Biopolym. Cell. 2021; 37(1):3-13.
http://dx.doi.org/10.7124/bc.000A47
Structure and Function of Biopolymers
PH domain of BCR provides colocalization of full-length BCR with centrosome together with cortactin to facilitate actin-organizing function
1Gurianov D. S., 1Antonenko S. V., 1Telegeev G. D.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143

Abstract

Chromosomal translocation between 9 and 22 chromosomes leads to the fusion of bcr and abl genes. Because of different breakpoints in bcr gene three forms of chimeric BCR-ABL proteins exist – p230, p210, and p190. BCR-ABLp190 lacks Pleckstrin homology (PH) domain of BCR and is associated with acute lymphoblastic leukaemia. In contrast, BCR-ABLp210 has PH domain and occurs during chronic myeloblastic leukaemia. BCR-ABL can bind to centrosomes, which function as a regulating center of cell division and spindle formation during mitosis. Cortactin, the main function of which is actin branching, was previously identified by mass-spectrometry as one of the potential partners interacting with the PH domain of BCR. Aim. To determine whether BCR and cortactin colocalize with centrosomes and to study a possible role of PH domain in such colocalization. Methods. Mammalian cell culturing, immunofluorescence analysis, fluorescent microscopy of live cells. Results. In the present work we show that both full-length BCR protein and PH domain colocalize with centrosome together with cortactin in live HEK293T cells. We also demonstrate that BCR colocalizes with γ-tubulin and the points of actin branching in fixed K562 cells. Using anti-ABL and anti-BCR antibodies we also show that colocalization with the actin branching center is typical for BCR-ABL and BCR, but not for ABL alone. Conclusions. PH domain of BCR is required for colocalization of BCR or BCR-ABL with centrosome. Together with cortactin, BCR-ABL can affect centrosome function through deregulation of actin branching or abnormal phosphorylation, which can be a matter of further research.
Keywords: BCR-ABL, centrosome, cortactin, CML
Full text: (PDF, in English)

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