Heidelberg University Biochemistry Center, Germany.
FEBS Lett. 2021 Jun;595(12):1639-1655. doi: 10.1002/1873-3468.14097. Epub 2021 May 12.
MXDs are transcription repressors that antagonize MYC-mediated gene activation. MYC, when associated with MIZ1, acts also as a repressor of a subset of genes, including p15 and p21. A role for MXDs in regulation of MYC-repressed genes is not known. We report that MXDs activate transcription of p15 and p21 in U2OS cells. This activation required DNA binding by MXDs and their interaction with MIZ1. MXD mutants deficient in MIZ1 binding interacted with the MYC-binding partner MAX and were active as repressors of MYC-activated genes but failed to activate MYC-repressed genes. Mutant MXDs with reduced DNA-binding affinity interacted with MAX and MIZ1 but neither repressed nor activated transcription. Our data show that MXDs and MYC have a reciprocally antagonistic potential to regulate transcription of target genes.
MXDs 是转录抑制剂，可拮抗 MYC 介导的基因激活。当 MYC 与 MIZ1 结合时，也可以作为包括 p15 和 p21 在内的一组基因的抑制剂。MXD 在调节 MYC 抑制基因中的作用尚不清楚。我们报告称，MXD 在 U2OS 细胞中激活 p15 和 p21 的转录。这种激活需要 MXD 通过 DNA 结合及其与 MIZ1 的相互作用。缺乏与 MIZ1 结合的 MXD 突变体与 MYC 结合伙伴 MAX 相互作用，并作为 MYC 激活基因的抑制剂发挥作用，但不能激活 MYC 抑制基因。与 DNA 结合亲和力降低的突变 MXD 与 MAX 和 MIZ1 相互作用，但既不抑制也不激活转录。我们的数据表明，MXD 和 MYC 具有相互拮抗的潜力，可调节靶基因的转录。
