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OPPOSING ACTIONS OF C-ETS PU.1 AND C-MYB PROTOONCOGENE PRODUCTS IN REGULATING THE MACROPHAGE-SPECIFIC PROMOTERS OF THE HUMAN AND MOUSE COLONY-STIMULATING FACTOR-I RECEPTOR (C-FMS) GENES
被引:110
作者:
REDDY, MA
YANG, BS
YUE, X
BARNETT, CJK
ROSS, IL
SWEET, MJ
HUME, DA
OSTROWSKI, MC
机构:
[1] DUKE UNIV, MED CTR, DEPT MICROBIOL, DURHAM, NC 27710 USA
[2] UNIV QUEENSLAND, CTR MOLEC BIOL & BIOTECHNOL, ST LUCIA, QLD 4072, AUSTRALIA
关键词:
D O I:
10.1084/jem.180.6.2309
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
The receptor for macrophage colony stimulating factor (CSF-1), the c-fms gene product, is a key determinant in the differentiation of monocytic phagocytes. Dissection of the human and mouse c-fms proximal promoters revealed opposing roles for nuclear protooncogenes in the transcriptional regulation of this gene. On the one hand, c-ets-1, c-ets-2, and the macrophage-specific factor PU.1, but not the ets-factor PEA3, trans-activated the c-fms proximal promoter. On the other hand c-myb repressed proximal promoter activity in macrophages and blocked the action of c-ets-1 and c-ets-2. Basal c-fms promoter activity was almost undetectable in the M1 leukaemia line, which expressed high levels of c-myb, but was activated as cells differentiated in response to leukemia inhibitory factor and expressed c-fms mRNA. The repressor function of c-myb depended on the COOH-terminal domain of the protein. We propose that ets-factors are necessary for the tissue-restricted expression of c-fms and that c-myb acts to ensure correct temporal expression of c-fms during myeloid differentiation.
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页码:2309 / 2319
页数:11
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