MYB AND ETS PROTEINS COOPERATE TO TRANSACTIVATE AN EARLY MYELOID GENE

被引:91
作者
SHAPIRO, LH
机构
[1] Department of Experimental Oncology, St. Jude Children's Res. Hospital, Memphis
关键词
D O I
10.1074/jbc.270.15.8763
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The earliest progenitor cell committed to the granulocyte/monocyte developmental pathway can be identified by the appearance of a 150-kDa glycoprotein on the cell surface (CD13/aminopeptidase N (CD13/APN), EC 3.4.11.2). A 455-base pair genomic fragment from the CD13/APN gene containing a Myb consensus-binding site as well as three potential Ets-binding sites was found to regulate tissue-appropriate expression of reporter genes in hematopoietic cell lines. Transactivation experiments with plasmids expressing either a full-length or truncated Myb protein and the full-length Ets-1 or Ets-2 protein demonstrated that these proteins cooperate to positively regulate CD13/APN gene expression. This cooperation is synergistic, as levels of transcriptional activity produced by Myb and Ets in combination were higher than those expected from a purely additive effect. Mutation of the Myb consensus-binding site completely abolished CD13/APN promoter activity in myeloid cells. Introduction of a dominant interfering Myb allele disrupted the ability of endogenous c-Myb in myeloid cells to transactivate the CD13/APN construct. Other myeloid cell-expressed Ets family members (PU.1, Fli-1, and Elf-1) failed to produce a cooperative transactivating effect when combined with the Myb expression construct. These data contrast with previous studies indicating that full-length c-Myb is unable to positively cooperate with Ets proteins in the regulation of myeloid genes. Because intact c-Myb and Ets-g proteins, both endogenously expressed in myeloid cells, act synergistically to transactivate the CD13/APN promoter, this gene may represent a physiological target for dissection of the roles of these transcription factors in normal and malignant myelopoiesis.
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页码:8763 / 8771
页数:9
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