Overexpression of PU.1 induces growth and differentiation inhibition and apoptotic cell death in murine erythroleukemia cells.
Overexpression of PU.1 induces growth and differentiation inhibition and apoptotic cell death in murine erythroleukemia cells.
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PU.1 的过度表达会诱导小鼠红白血病细胞的生长和分化抑制以及细胞凋亡。
作者：
Toshiyuki Yamada;N. Kondoh;Mana Matsumoto;Midori Yoshida;A. Maekawa;T. Oikawa
PU.1是ets转录因子家族的成员，在Friend病毒诱导的小鼠红细胞白血病（MEL）细胞中表达，这是由于前病毒整合到PU.1/Spi-1位点的结果。二甲基亚砜（DMSO）诱导MEL细胞分化后，PU.1/Spi-1基因的表达在诱导β -珠蛋白基因表达之前降低。通过锌诱导表达质粒在MEL细胞中过表达PU.1，导致了意外的生长抑制。用DMSO处理过表达pu .1的转染后，细胞生长受到明显抑制，并诱导细胞凋亡。在此条件下，β -珠蛋白基因未被诱导表达。无论DMSO是否存在，表达激活结构域或dna结合et结构域缺失的突变PU.1蛋白后，MEL细胞都不会诱导生长抑制或凋亡。有趣的是，β -珠蛋白基因在表达前一种突变体的转染物中没有被诱导表达，而在DMSO存在的情况下，表达后一种突变体的转染物中却被诱导表达。这些结果表明，MEL细胞中PU.1的过表达导致生长和分化受到抑制，并与DMSO一起导致凋亡细胞死亡。这些结果还表明，PU.1的激活结构域和Ets结构域对这些效应的诱导有不同的作用。
PU.1 is a member of the ets family of transcription factors and is expressed in Friend virus-induced murine erythroleukemia (MEL) cells as a consequence of proviral integration into the PU.1/Spi-1 locus. After induction of MEL cell differentiation by treatment with dimethylsulfoxide (DMSO), expression of the PU.1/Spi-1 gene decreased before induction of beta-globin gene expression. Overexpression of PU.1 by using a zinc-inducible expression plasmid in MEL cells resulted in unexpected growth inhibition of the transfectants. When PU.1-overexpressing transfectants were treated with DMSO, growth inhibition became much pronounced and apoptosis was induced. Expression of the beta-globin gene was not induced under this condition. Neither growth inhibition nor apoptosis was induced in MEL cells after expression of mutant PU.1 proteins with a deletion of the activation domain or the DNA-binding Ets domain irrespective of the presence of DMSO. Interestingly, beta-globin gene expression was not induced in the transfectants expressing the former mutant, whereas it was induced in those expressing the latter one in the presence of DMSO. These results indicate that overexpression of PU.1 in MEL cells results in growth and differentiation inhibition and, in conjunction with DMSO treatment, apoptotic cell death. These results also suggest that the activation domain and the Ets domain of PU.1 contribute differently to induction of these effects.
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影响因子：
56.9
作者：
SCOTT, EW;SIMON, MC;SINGH, H
通讯作者：
SINGH, H
Friend 病毒 gp55 和促红细胞生成素激活促红细胞生成素受体，并通过鼠 Fv-2r 抗性基因下调。
DOI：
10.1073/pnas.87.24.9985
发表时间：
1990
影响因子：
11.1
作者：
Hoatlin,ME;Kozak,SL;Lilly,F;Chakraborti,A;Kozak,CA;Kabat,D
通讯作者：
Kabat,D
Ets 相关蛋白 PU.1 通过新型 Ets 结合元件调节免疫球蛋白 J 链基因的表达。
影响因子：
10.5
作者：
Shin,MK;Koshland,ME
通讯作者：
Koshland,ME
影响因子：
56.9
作者：
PONGUBALA, JMR;VANBEVEREN, C;ATCHISON, ML
通讯作者：
ATCHISON, ML
ETS 结构域蛋白对淋巴特异性免疫球蛋白 mu 重链基因增强子的调节。
DOI：
10.1126/science.8316859
发表时间：
1993
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nelsen,B;Tian,G;Erman,B;Gregoire,J;Maki,R;Graves,B;Sen,R
通讯作者：
Sen,R