Figure 8.

Models of MNT fates and biological roles depending on MAX. A, in MAX-expressing cells, most of the MNT is retained in the cell nucleus where it limits its own expression. In MAX-deficient cells as UR61, MNT is distributed in nucleus and cytoplasm and is unable to bind the promoter and regulate its transcriptional activity. The model includes the presence of MNT–MNT homodimers and the interaction MNT–MLX in the cytoplasm, which might be responsible for the MNT partial localization in the cytoplasm in MAX-deficient cells. B, model of the biological roles of MNT independent of MAX in UR61 cells. With physiological MNT levels, MNT homodimers and MNT–MLX heterodimers are enhancing cell cycle progression through direct regulation of CDK1 and BIRC5, and DNA repair through BRCA1-dependent mechanisms. However, upon MNT knockdown, this regulation is impaired, with a decrease in CDK1, BIRC5, and BRCA1 and increased levels of CDKN1C, E2F6, and ERCC6. This would cause a cell cycle arrest and the activation of ERCC6-dependent DNA repair mechanisms.