The novel primary response gene MyD118 and the proto-oncogenes myb, myc, and bcl-2 modulate transforming growth factor beta 1-induced apoptosis of myeloid leukemia cells.
The novel primary response gene MyD118 and the proto-oncogenes myb, myc, and bcl-2 modulate transforming growth factor beta 1-induced apoptosis of myeloid leukemia cells.
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新型初级反应基因 MyD118 和原癌基因 myb、myc 和 bcl-2 调节转化生长因子 β 1 诱导的骨髓性白血病细胞凋亡。
DOI：
10.1128/mcb.14.4.2352-2360.1994
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发表时间：
1994
影响因子：
5.3
通讯作者：
Hoffman,B
中科院分区：
文献类型：
--
作者：
Selvakumaran,M;Lin,HK;Sjin,RT;Reed,JC;Liebermann,DA;Hoffman,B
细胞数量受增殖、生长停滞和程序性细胞死亡之间的平衡调节。细胞稳态的一个深刻的例子，控制整个生命，是血细胞发育的复杂过程，但很少了解细胞内机制，调节血细胞生长停滞和程序性细胞死亡。本研究以转化生长因子β1（transforming growth factor β1，TGFβ1）处理的M1髓系白血病细胞和基因工程改造的M1细胞为研究对象，探讨了M1细胞生长停滞和凋亡的调控机制。MyD 118是一种新的分化初级反应基因，也是TGFβ1诱导的初级反应基因，阻断其早期表达可延迟TGFβ1诱导的细胞凋亡，表明MyD 118是TGFβ1介导的细胞死亡的正性调节因子。bcl-2的高表达阻断了TGFβ1诱导的细胞凋亡途径，但不能阻断TGFβ1诱导的细胞生长停滞。c-myb或c-myb的表达失调抑制生长停滞并加速凋亡，首次证明c-myb在调节凋亡中起作用。在所有情况下，凋亡反应与MyD 118表达水平相关。这些结果表明，主要反应基因MyD 118与c-myc、c-myb和bcl-2原癌基因相互作用，调节髓系细胞的生长停滞和凋亡。
Cell numbers are regulated by a balance among proliferation, growth arrest, and programmed cell death. A profound example of cell homeostasis, controlled throughout life, is the complex process of blood cell development, yet little is understood about the intracellular mechanisms that regulate blood cell growth arrest and programmed cell death. In this work, using transforming growth factor β1 (TGFβ1)-treated M1 myeloid leukemia cells and genetically engineered M1 cell variants, the regulation of growth arrest and apoptosis was dissected. Blocking of early expression ofMyD118, a novel differentiation primary response gene also shown to be a primary response gene induced by TGFβ1, delayed TGFβ1-induced apoptosis, demonstrating thatMyD118is a positive modulator of TGFβ1-mediated cell death. Elevated expression ofbcl-2blocked the TGFβ1-induced apoptotic pathway but not growth arrest induced by TGFβ1. Deregulated expression of either c-mycor c-mybinhibited growth arrest and accelerated apoptosis, demonstrating for the first time that c-mybplays a role in regulating apoptosis. In all cases, the apoptotic response was correlated with the level ofMyD118expression. Taken together, these findings demonstrate that the primary response geneMyD118and the c-myc, c-myb, andbcl-2proto-oncogenes interact to modulate growth arrest and apoptosis of myeloid cells.