The c-Myb gene encodes the p75c-Mybisoform and less-abundant proteins generated by alternatively spliced transcripts. Among these, the best known is p89c-Mybex9b, which contains 121 additional amino acids between exon 9 and 10, in a domain involved in protein-protein interactions and negative regulation. In hematopoietic cells, expression of p89c-Mybex9baccounts for 10-15% of total c-Myb; these levels may be biologically relevant because modest changes in c-Myb expression affects proliferation and survival of leukemic cells and lineage choice and frequency of normal hematopoietic progenitors. In this study, we assessed biochemical activities of p89c-Mybex9band the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75c-Myb, p89c-Mybex9bis more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of p89c-Mybex9benhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of p89c-Mybex9breduced proliferation and colony formation, enhanced IM sensitivity of K562 cells and markedly suppressed colony formation of CML CD34+cells, without affecting the levels of p75c-Myb. Together, these studies indicate that expression of the low-abundance p89c-Mybex9bisoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells. © 2012 Macmillan Publishers Limited All rights reserved.
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Manzotti, G., Mariani, S. A., Corradini, F., Bussolari, R., Cesi, V., Vergalli, J., ... Calabretta, B. (2012). Expression of p89 c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells. Blood Cancer Journal, 2(5), -. [e71]. https://doi.org/10.1038/bcj.2012.16