XB-FEAT-854080

foxm1

This is the community wiki page for the gene foxm1 please feel free to add any information that is relevant to this gene that is not already captured elsewhere in Xenbase.

role of foxm1 , quoted from conclusions in XB-art-35292

Our current understanding of FoxM1 has given it a central role in the regulation of the cell division process. FoxM1 executes this function primarily through regulation of essential mitotic regulatory proteins that are part of the G2/M transcriptional cluster of mammalian cells. Nonetheless, many of the targets of FoxM1 have currently no cell cycle regulatory function ascribed to them and it will be interesting to find out if any of these do regulate cell division. Alternatively, FoxM1 may have additional roles besides regulation of cell division. In this respect, one of its main target genes, Gas1, has been associated with cellular quiescence and is implicated in Sonic Hedgehog (Shh) signaling. As FoxM1 itself was shown to be regulated by Gli-transcription factors, which in turn are responsive to Shh, this opens the door to a feedback system that could play an important role during the developmental processes driven by Shh, such as brain development. However, it should be noted, that Gas1 has been annotated as part of the G2/M cluster in human cells, suggesting Gas1 may also be a mitotic target of FoxM1 with a role in mitosis that awaits discovery.

Besides the undiscovered roles of FoxM1 target genes, the regulation of FoxM1 itself also holds many remaining mysteries. It is currently not understood how exactly FoxM1 activity is restricted during an ongoing cell cycle. Also, it remains to be addressed whether FoxM1 alone, or, like its ancestor Fhk1/2 in yeast, in complex with other transcription factors acts to transactivate its target genes.

Another aspect of FoxM1 that will have to be addressed in the future is its role during ageing. Clearly, FoxM1 activity is reduced as cells age, but how this comes about is completely unclear. On the other hand, ectopic expression of FoxM1 can revert some of the proliferation defects that come with age, but it remains to be seen if overall age can be affected by altering FoxM1 expression. In parallel, if and how the function of FoxM1 is affected during tumorigenesis is not well understood. FoxM1 expression appears to be often elevated in cancer cells, whether this is a direct cause for cellular transformation is still unclear, and seems an interesting avenue to explore.