First Author | Walker W | Year | 2005 |
Journal | J Cell Biol | Volume | 169 |
Issue | 3 | Pages | 405-13 |
PubMed ID | 15866886 | Mgi Jnum | J:100223 |
Mgi Id | MGI:3587497 | Doi | 10.1083/jcb.200411013 |
Citation | Walker W, et al. (2005) Mnt-Max to Myc-Max complex switching regulates cell cycle entry. J Cell Biol 169(3):405-13 |
abstractText | The c-Myc oncoprotein is strongly induced during the G0 to S-phase transition and is an important regulator of cell cycle entry. In contrast to c-Myc, the putative Myc antagonist Mnt is maintained at a constant level during cell cycle entry. Mnt and Myc require interaction with Max for specific DNA binding at E-box sites, but have opposing transcriptional activities. Here, we show that c-Myc induction during cell cycle entry leads to a transient decrease in Mnt-Max complexes and a transient switch in the ratio of Mnt-Max to c-Myc-Max on shared target genes. Mnt overexpression suppressed cell cycle entry and cell proliferation, suggesting that the ratio of Mnt-Max to c-Myc-Max is critical for cell cycle entry. Furthermore, simultaneous Cre-Lox mediated deletion of Mnt and c-Myc in mouse embryo fibroblasts rescued the cell cycle entry and proliferative block caused by c-Myc ablation alone. These results demonstrate that Mnt-Myc antagonism plays a fundamental role in regulating cell cycle entry and proliferation. |