| CK2 is an ubiquitously expressed, constitutively active protein kinase with over 300 target substrates identified to date. It has been shown to be upregulated and overexpressed in numerous cancer cell lines and primary tumors. Inhibition of CK2 accelerates apoptosis. Sumo1 is an ubiquitously expressed, small protein that is covalently and reversibly attached to protein substrates post-translationally. Using various in vivo cell biology techniques and imaging, as well as in vitro biochemical assays, we have shown several results regarding CK2 regulation, especially during apoptosis, as well as identified a novel substrate of CK2 phosphorylation: Sumo1. We have shown that CK2A1 is alternatively spliced and that its splice variant, having no intrinsic kinase activity, is inhibitory of CK2 activity in vitro. We have further shown that CK2 activity is altered during type-II fas-mediated apoptosis by segregating CK2A1 to the nucleus, allowing apoptosis to proceed. Lastly, we have shown that Sumo1, but not Sumo2 or ubiquitin, can be phosphorylated by CK2. This is the first demonstration of a post-translational modification of any ubiquitin-like modifier. Furthermore, CK2-mediated phosphorylation of Sumo1 is pro-survival. |
