Sci. Signal., 10 May 2011
Protection from DeathCaspases are cysteine-dependent proteases that cleave target proteins—including other caspases—at aspartate residues within caspase recognition motifs. Caspase-3, which operates at the point of convergence of extrinsic and intrinsic cell death pathways, is generated as a proenzyme that must be cleaved by upstream caspases to become activated. Noting that phosphorylation of caspase substrates at residues near the caspase recognition motif protects them from cleavage (see the Perspective by Filhol and Cochet), Duncan et al. scanned the human proteome for sequences that contained overlapping target sites for caspases and any of 10 kinases implicated in promoting cell survival or tumorigenesis. The protein kinase CK2 emerged as the kinase with the greatest number of such overlapping sequences, and potential targets of CK2 and caspases were evaluated by a newly developed technique for identifying caspase substrates. In addition to phosphorylating targets of caspase-3, CK2 also phosphorylated procaspase-3, thereby blocking its activation by upstream caspases and thus protecting cells from apoptosis. Together, these data suggest a global role for CK2 in preventing apoptosis, which may underlie its role in tumorigenesis.
Citation: J. S. Duncan, J. P. Turowec, K. E. Duncan, G. Vilk, C. Wu, B. Lüscher, S. S.- C. Li, G. B. Gloor, D. W. Litchfield, A Peptide-Based Target Screen Implicates the Protein Kinase CK2 in the Global Regulation of Caspase Signaling. Sci. Signal. 4, ra30 (2011).
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