| First Author | Laoukili J | Year | 2008 |
| Journal | Mol Cell Biol | Volume | 28 |
| Issue | 9 | Pages | 3076-87 |
| PubMed ID | 18285455 | Mgi Jnum | J:135663 |
| Mgi Id | MGI:3794242 | Doi | 10.1128/MCB.01710-07 |
| Citation | Laoukili J, et al. (2008) Activation of FoxM1 during G2 requires cyclin A/Cdk-dependent relief of autorepression by the FoxM1 N-terminal domain. Mol Cell Biol 28(9):3076-87 |
| abstractText | The Forkhead transcription factor FoxM1 is an important regulator of gene expression during the G(2) phase. Here, we show that FoxM1 transcriptional activity is kept low during G(1)/S through the action of its N-terminal autoinhibitory domain. We found that cyclin A/cdk complexes are required to phosphorylate and activate FoxM1 during G(2) phase. Deletion of the N-terminal autoinhibitory region of FoxM1 generates a mutant of FoxM1 (DeltaN-FoxM1) that is active throughout the cell cycle and no longer depends on cyclin A for its activation. Mutation of two cyclin A/cdk sites in the C-terminal transactivation domain leads to inactivation of full-length FoxM1 but does not affect the transcriptional activity of the DeltaN-FoxM1 mutant. We show that the intramolecular interaction of the N- and C-terminal domains depends on two RXL/LXL motifs in the C terminus of FoxM1. Mutation of these domains leads to a similar gain of function as deletion of the N-terminal repressor domain. Based on these observations we propose a model in which FoxM1 is kept inactive during the G(1)/S transition through the action of the N-terminal autorepressor domain, while phosphorylation by cyclin A/cdk complexes during G(2) results in relief of inhibition by the N terminus, allowing activation of FoxM1-mediated gene transcription. |
