Title | Expression of p89 c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells |
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Publication Type | Articolo su Rivista peer-reviewed |
Year of Publication | 2012 |
Authors | Manzotti, G., Mariani S.A., Corradini F., Bussolari R., Cesi Vincenzo, Vergalli J., Ferrari-Amorotti G., Fragliasso V., Soliera A.R., Cattelani S., Raschellà G., Holyoake T.L., and Calabretta B. |
Journal | Blood Cancer Journal |
Volume | 2 |
ISSN | 20445385 |
Keywords | alternative RNA splicing, article, BCR ABL protein, cancer cell culture, CD34 selection, cell proliferation, cell strain k 562, Cell Survival, Cell Transformation, Chronic myeloid leukemia, colony formation, controlled study, down regulation, drug sensitivity, human, human cell, imatinib, leukemia cell, p89 c mybex9b protein, promoter region, protein c Myb, protein expression, stem cell, transactivation, unclassified drug |
Abstract | The c-Myb gene encodes the p75 c-Myb isoform and less-abundant proteins generated by alternatively spliced transcripts. Among these, the best known is p89 c-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 p89 c-Mybex9b accounts 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 p89 c-Mybex9b and the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75 c-Myb, p89 c-Mybex9b is more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of p89 c-Mybex9b enhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of p89 c-Mybex9b reduced proliferation and colony formation, enhanced IM sensitivity of K562 cells and markedly suppressed colony formation of CML CD34 + cells, without affecting the levels of p75 c-Myb. Together, these studies indicate that expression of the low-abundance p89 c-Mybex9b isoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells. © 2012 Macmillan Publishers Limited All rights reserved. |
Notes | cited By 12 |
URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864046723&doi=10.1038%2fbcj.2012.16&partnerID=40&md5=3a87dbe78207c42ff345bf8a8692e2d7 |
DOI | 10.1038/bcj.2012.16 |
Citation Key | Manzotti2012 |