PMID:24743732

Citation	Chen, H, Huang, S, Han, X, Zhang, J, Shan, C, Tsang, YH, Ma, HT and Poon, RY (2014) Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death. Cell Death Dis 5:e1177
Abstract	Many mitotic kinases are both critical for maintaining genome stability and are important targets for anticancer therapies. We provide evidence that SIK3 (salt-inducible kinase 3), an AMP-activated protein kinase-related kinase, is important for mitosis to occur properly in mammalian cells. Downregulation of SIK3 resulted in an extension of mitosis in both mouse and human cells but did not affect the DNA damage checkpoint. Time-lapse microscopy and other approaches indicated that mitotic exit but not mitotic entry was delayed. Although repression of SIK3 alone simply delayed mitotic exit, it was able to sensitize cells to various antimitotic chemicals. Both mitotic arrest and cell death caused by spindle poisons were enhanced after SIK3 depletion. Likewise, the antimitotic effects due to pharmacological inhibition of mitotic kinases including Aurora A, Aurora B, and polo-like kinase 1 were enhanced in the absence of SIK3. Finally, in addition to promoting the sensitivity of a small-molecule inhibitor of the mitotic kinesin Eg5, SIK3 depletion was able to overcome cells that developed drug resistance. These results establish the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target.
Links	PubMed PMC4001308 Online version:10.1038/cddis.2014.154
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:SIK3	Contributes to	GO:0045840: positive regulation of mitosis	ECO:0000315:		P		Figure 2 and figure 3	complete

References

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