The multiple functions of kinesin-4 family motor protein KIF4 and its clinical potential.

Human KIF4 is a member of Kinesin-4 kinesin family. The highly conserved structure contains an N-terminal motor region, coiled-coil region and C-terminal loading region. KIF4 plays important roles in DNA repair and DNA replication, which maintains genetic stability. KIF4 is also essential for regulation of mitosis and meiosis. KIF4 cooperates with condensin I and TopoIIα to help with chromosomal condensation, and binds to a plethora of cell-cycle proteins to regulate spindle organization and cytokinesis. Additionally, KIF4 plays roles in germ plasm aggregation and radial order in germ cells. In neuronal cells, KIF4 promotes proper axon growth by transporting substrates P0 and L1 to their proper location. Interestingly, KIF4 is abnormally expressed in a variety of cancers, where KIF4 is often up-regulated but can also be down-regulated in some cancers. This suggests distinctive regulatory mechanisms for different cancers. Recent studies support important roles for KIF4 in cancers such as the promotion of drug resistance or inhibition of apoptosis. Previous studies showed that by inhibiting or enhancing the expression of KIF4, the proliferation of cancer cells can be significantly reduced. Therefore KIF4 has potential as a therapeutic target for cancer therapy. Moreover, the misregulation of KIF4 is related to viral infection and neural system diseases like Alzheimer. We believe better understanding of this protein will help us develop better therapies for the diseases mentioned above. Here, we summarize KIF4 functions in normal cells and in various cancers, and provide an overview on the association between KIF4 disorders and disease progression.