A SWITCH FROM MYC-MAX TO MAD-MAX HETEROCOMPLEXES ACCOMPANIES MONOCYTE/MACROPHAGE DIFFERENTIATION
A SWITCH FROM MYC-MAX TO MAD-MAX HETEROCOMPLEXES ACCOMPANIES MONOCYTE/MACROPHAGE DIFFERENTIATION
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DOI：
10.1101/gad.7.11.2110
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发表时间：
1993-11-01
影响因子：
10.5
通讯作者：
EISENMAN, RN
中科院分区：
文献类型：
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作者：
AYER, DE;EISENMAN, RN
Mad 是一种碱性螺旋环螺旋拉链蛋白，在体外与 Max 形成异二聚体。 Mad:Max 异二聚体识别与 Myc:Max 异二聚体相同的 E-box 相关 DNA 结合位点。然而，在瞬时转染测定中，Myc 和 Mad 通过与 Max 相互作用以相反的方式影响转录。 Myc 激活，而 Mad 抑制转录。在这里，我们证明 Mad 蛋白在骨髓谱系细胞分化时被快速诱导。 Mad 蛋白在人体细胞中合成为 35 kD 核磷蛋白，半衰期极短（t1/2 = 15-30 分钟），并且可以在体内与 Max 形成复合物进行检测。在未分化的 U937 单核细胞系中，发现 Max 与 Myc 复合，但 Mad 不复合。然而，Mad:Max 复合物早在用 TPA 诱导巨噬细胞分化后 2 小时就开始积累。 TPA 处理后 48 小时，仅可检测到 Mad:Max 复合物。这些数据表明分化伴随着Max杂合物组成的变化。我们推测异源复合物的这种转换导致细胞增殖所需的 Myc:Max 靶基因的转录调控发生变化。
Mad is a basic-helix-loop-helix-zipper protein that heterodimerizes with Max in vitro. Mad:Max heterodimers recognize the same E-box-related DNA-binding sites as Myc:Max heterodimers. However, in transient transfection assays Myc and Mad influence transcription in opposite ways through interaction with Max; Myc activates while Mad represses transcription. Here, we demonstrate that Mad protein is induced rapidly upon differentiation of cells of the myeloid lineage. The Mad protein is synthesized in human cells as a 35-kD nuclear phosphoprotein with an extremely short half-life (t1/2 = 15-30 min) and can be, detected in vivo in a complex with Max. In the undifferentiated U937 monocyte cell line Max was found complexed with Myc but not Mad. However, Mad:Max complexes began to accumulate as early as 2 hr after induction of macrophage differentiation with TPA. By 48 hr following TPA treatment only Mad:Max complexes were detectable. These data show that differentiation is accompanied by a change in the composition of Max heterocomplexes. We speculate that this switch in heterocomplexes results in a change in the transcriptional regulation of Myc:Max target genes required for cell proliferation.