| First Author | Mathsyaraja H | Year | 2019 |
| Journal | Genes Dev | Volume | 33 |
| Issue | 17-18 | Pages | 1252-1264 |
| PubMed ID | 31395740 | Mgi Jnum | J:284176 |
| Mgi Id | MGI:6390691 | Doi | 10.1101/gad.325878.119 |
| Citation | Mathsyaraja H, et al. (2019) Max deletion destabilizes MYC protein and abrogates Emicro-Myc lymphomagenesis. Genes Dev 33(17-18):1252-1264 |
| abstractText | Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion of Max has a modest effect on B-cell development but completely abrogates Emicro-Myc-driven lymphomagenesis. While Max loss affects only a few hundred genes in normal B cells, it leads to the global down-regulation of Myc-activated genes in premalignant Emicro-Myc cells. We show that the balance between MYC-MAX and MNT-MAX interactions in B cells shifts in premalignant B cells toward a MYC-driven transcriptional program. Moreover, we found that MAX loss leads to a significant reduction in MYC protein levels and down-regulation of direct transcriptional targets, including regulators of MYC stability. This phenomenon is also observed in multiple cell lines treated with MYC-MAX dimerization inhibitors. Our work uncovers a layer of Myc autoregulation critical for lymphomagenesis yet partly dispensable for normal development. |
