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Expression of p89 c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells

TitoloExpression of p89 c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2012
AutoriManzotti, 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.
RivistaBlood Cancer Journal
Volume2
ISSN20445385
Parole chiavealternative 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.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84864046723&doi=10.1038%2fbcj.2012.16&partnerID=40&md5=3a87dbe78207c42ff345bf8a8692e2d7
DOI10.1038/bcj.2012.16
Citation KeyManzotti2012