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An N-terminal inhibitory domain modulates activity of FoxM1 during cell cycle
| Content Provider | CiteSeerX |
|---|---|
| Abstract | The FoxM1 transcription factor plays critical roles in the expression of genes that are essential for cell proliferation. FoxM1 null or depleted cells fail to progress through mitosis, as expression of several mitotic genes depends upon FoxM1. The transcriptional activity of FoxM1 is stimulated by cyclin-cdk-mediated phosphorylation at a site within the transcriptional activation domain. Here, we characterize the role of an N-terminal inhibitory domain in the transcriptional activity of FoxM1. Deletion of the N-terminal 232 amino-acid residues increases the transcriptional and transforming activities of FoxM1. Moreover, while the activity of the full-length FoxM1 is stimulated by growth factors, the activity of the N-terminal deletion mutant is constitutively high in all phases of the cell cycle. The N-terminal deletion also eliminates the requirement for cyclin-cdk to activate FoxM1. We provide evidence that the N-terminal domain interacts with the C-terminal half of the transcription factor to attenuate its transcriptional activity. Moreover, the N-terminal fragment inhibits the transcriptional activity of FoxM1 in G1/S cells, but not in G2/M cells. Our results suggest that cyclin-cdk phosphorylates FoxM1 to counteract the inhibition by the N-terminal domain to fully activate FoxM1 in G2/M phase. |
| File Format | |
| Access Restriction | Open |
| Subject Keyword | Transcriptional Activity Cell Cycle N-terminal Inhibitory Domain N-terminal Domain Interacts Foxm1 Transcription Factor Cyclin-cdk-mediated Phosphorylation Critical Role Transcriptional Activation Domain Growth Factor Cell Proliferation Cyclin-cdk Phosphorylates Foxm1 N-terminal Domain Full-length Foxm1 G2 Phase G2 Cell G1 Cell Transcription Factor N-terminal Deletion Mutant N-terminal Deletion N-terminal Fragment C-terminal Half Amino-acid Residue Transforming Activity Several Mitotic Gene Foxm1 Null |
| Content Type | Text |
