4x7q

Structural highlights

Function

PIM2_HUMAN Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression, the regulation of cap-dependent protein translation and through survival signaling by phosphorylation of a pro-apoptotic protein, BAD. Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase transcriptional activity. The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner and in parallel to the PI3K-Akt pathway. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Promotes cell survival in response to a variety of proliferative signals via positive regulation of the I-kappa-B kinase/NF-kappa-B cascade; this process requires phosphorylation of MAP3K8/COT. Isoform 1 is less active in this respect. Promotes growth factor-independent proliferation by phosphorylation of cell cycle factors such as CDKN1A and CDKN1B. Involved in the positive regulation of chondrocyte survival and autophagy in the epiphyseal growth plate.^{[1] [2] [3]}

See Also

• Serine/threonine protein kinase 3D structures

References

1. ↑ Morishita D, Katayama R, Sekimizu K, Tsuruo T, Fujita N. Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. Cancer Res. 2008 Jul 1;68(13):5076-85. doi: 10.1158/0008-5472.CAN-08-0634. PMID:18593906 doi:10.1158/0008-5472.CAN-08-0634
2. ↑ Gong J, Wang J, Ren K, Liu C, Li B, Shi Y. Serine/threonine kinase Pim-2 promotes liver tumorigenesis induction through mediating survival and preventing apoptosis of liver cell. J Surg Res. 2009 May 1;153(1):17-22. doi: 10.1016/j.jss.2008.03.033. Epub 2008, Apr 22. PMID:18675992 doi:http://dx.doi.org/10.1016/j.jss.2008.03.033
3. ↑ Wang Z, Zhang Y, Gu JJ, Davitt C, Reeves R, Magnuson NS. Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells. Int J Biochem Cell Biol. 2010 Jun;42(6):1030-8. doi:, 10.1016/j.biocel.2010.03.012. Epub 2010 Mar 20. PMID:20307683 doi:http://dx.doi.org/10.1016/j.biocel.2010.03.012
4. ↑ Ishchenko A, Zhang L, Le Brazidec JY, Fan J, Chong JH, Hingway A, Raditsis A, Singh L, Elenbaas B, Hong VS, Marcotte D, Silvian L, Enyedy I, Chao J. Structure-based design of low-nanomolar PIM kinase inhibitors. Bioorg Med Chem Lett. 2015 Feb 1;25(3):474-80. doi: 10.1016/j.bmcl.2014.12.041., Epub 2014 Dec 19. PMID:25575657 doi:http://dx.doi.org/10.1016/j.bmcl.2014.12.041