부산대학교 도서관

The Bcr protein was originally identified because of its fusion to Abl as a consequence of the Philadelphia chromosome translocation found in chronic myelogenous and acute lymphoblastic leukemias. The Bcr moiety is essential for the transforming activity of the Bcr/Abl oncogene. In search of physiologically relevant Bcr and Bcr/Abl-interacting proteins, we performed an interaction screen in yeast using the entire Bcr protein as bait. We here report that the α catalytic subunit of protein kinase CKII strongly and specifically forms a complex with Ber in yeast in mouse lysates. The region in Bcr responsible for CKIIα binding was localized to residues 242-413. CKIIα was previously shown to be involved in leukemogenesis and tumorigenesis using different experimental approaches including mouse models. Inhibition of Bcr/Abl P190 in lymphoma cells from Ber/Abl transgenic mice using imatinib reduced CKIIα activity. A highly selective inhibitor of CKIIα, 4,5.6.7-tetrabromo-2-benzotriazole, inhibited the growth of murine lymphoid cells with induced P210 Bcr/Abl expression and of P190 lymphoma cells. Our results demonstrate that CKIIα plays an important role in the proliferation of Bcr/Abl expressing cells and suggests that inhibitors of CKIIα may have therapeutic potential in the treatment of Bcr/Abl-positive leukemia patients. [ABSTRACT FROM AUTHOR]