文章：

p8^9c-Mybex9b是c-Myb的一种选择性剪接形式，其表达是表达p210BCR/ABL细胞增殖和存活所必需的

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

原文发布日期：2012-05-11

DOI: 10.1038/bcj.2012.16

类型: Original Article

开放获取: 是

英文摘要：

The c-Myb gene encodes the p75c-Myb isoform 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-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 p89c-Mybex9b and the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75c-Myb, p89c-Mybex9b is more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of p89c-Mybex9b enhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of p89c-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 p75c-Myb. Together, these studies indicate that expression of the low-abundance p89c-Mybex9b isoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells.

摘要翻译： 

c-Myb基因编码p75^c-Myb亚型及通过可变剪接转录本产生的少量其他蛋白。其中最为人熟知的是p89^c-Mybex9b，该亚型在第9和第10外显子之间包含额外121个氨基酸，该区域参与蛋白质相互作用及负向调控。在造血细胞中，p89^c-Mybex9b的表达量约占c-Myb总表达量的10-15%；这一水平可能具有生物学意义，因为c-Myb表达的微小变化就会影响白血病细胞的增殖存活、正常造血祖细胞的谱系选择与出现频率。本研究评估了p89^c-Mybex9b的生化活性及其在K562细胞和原代慢性髓系白血病（CML）祖细胞中表达扰动的影响。与p75^c-Myb相比，p89^c-Mybex9b具有更高稳定性，在反式激活Myb调控启动子时更有效。异位表达p89^c-Mybex9b可增强K562细胞增殖和集落形成能力并降低其对伊马替尼（IM）的敏感性；相反，特异性下调p89^c-Mybex9b能抑制K562细胞增殖和集落形成、增强其对IM的敏感性，并显著抑制CML CD34⁺细胞的集落形成，且不影响p75^c-Myb水平。这些研究共同表明，低丰度p89^c-Mybex9b亚型的表达对c-Myb在BCR/ABL转化细胞中的整体生物学效应具有重要作用。

原文链接：

Expression of p89c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells