The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor. Upon E-box binding, the MYC-MAX dimer activates gene expression. MNT also binds to the MAX dimerization protein MLX (MLX), and MNT-MLX and MNT-MAX dimers co-exist. However, all MNT functions have been attributed to MNT-MAX dimers, and no functions of the MNT-MLX dimer have been described. MNT's biological role has been linked to its function as a MYC oncogene modulator, but little is known about its regulation. We show here that MNT localizes to the nucleus of MAX-expressing cells and that MNT-MAX dimers bind and repress the MNT promoter, an effect that depends on one of the two E-boxes on this promoter. In MAX-deficient cells, MNT was overexpressed and redistributed to the cytoplasm. Interestingly, MNT was required for cell proliferation even in the absence of MAX. We show that in MAX-deficient cells, MNT binds to MLX, but also forms homodimers. RNA-sequencing experiments revealed that MNT regulates the expression of several genes even in the absence of MAX, with many of these genes being involved in cell cycle regulation and DNA repair. Of note, MNT-MNT homodimers regulated the transcription of some genes involved in cell proliferation. The tight regulation of MNT and its functionality even without MAX suggest a major role for MNT in cell proliferation.

中文翻译：

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MNT 转录因子自动调节其表达并支持 MYC 相关 X 因子 (MAX) 缺陷细胞的增殖。

MAX 网络转录阻遏蛋白 (MNT) 是基本螺旋-环-螺旋 (bHLH) 家族的 MXD 家族转录因子。MNT 与另一种转录调节因子 MYC 相关因子 X (MAX) 形成二聚体，并通过与 E-box 结合来下调基因。MAX 还与 MYC（一种致癌 bHLH 转录因子）形成二聚体。与 E-box 结合后，MYC-MAX 二聚体激活基因表达。MNT 还与 MAX 二聚蛋白 MLX (MLX) 结合，MNT-MLX 和 MNT-MAX 二聚体共存。然而，所有MNT功能都归因于MNT-MAX二聚体，并且没有描述MNT-MLX二聚体的功能。MNT 的生物学作用与其作为 MYC 癌基因调节剂的功能有关，但对其调节作用知之甚少。我们在这里表明，MNT 定位于 MAX 表达细胞的细胞核，并且 MNT-MAX 二聚体结合并抑制 MNT 启动子，这种效应取决于该启动子上的两个 E-box 之一。在 MAX 缺陷的细胞中，MNT 过度表达并重新分布到细胞质。有趣的是，即使在没有 MAX 的情况下，细胞增殖也需要 MNT。我们发现，在 MAX 缺陷细胞中，MNT 与 MLX 结合，但也形成同型二聚体。RNA测序实验表明，即使在没有MAX的情况下，MNT也能调节多个基因的表达，其中许多基因参与细胞周期调节和DNA修复。值得注意的是，MNT-MNT 同二聚体调节一些参与细胞增殖的基因的转录。即使没有 MAX，MNT 及其功能的严格调节表明 MNT 在细胞增殖中发挥着重要作用。