70. Substrate screening identifies a novel target sequence for the proteasomal activity regulated by ionizing radiation
    A. Broggini-Tenzer, A. Hollenstein, Z. Pianowski, A. Wampfler, P. Furmanova, N. Winssinger, M. Pruschy
    Proteomics 2010, 10, 304-314

The screening for treatment-induced enzyme activities offers the opportunity to discover important regulatory mechanisms and the identification of potential targets for anti-cancer therapies. A novel screening technique was applied to screen substrate peptide sequences for proteolytic activities up- or down-regulated by ionizing radiation in tumor cells. One specific substrate sequence was cleaved in control cell extracts but to a smaller extent in irradiated cell extracts and investigated in detail. Based on protease-class-specific inhibitory studies and cleavage site analysis a potent warhead-inhibitor was synthesized and used to identify the proteasome as the protease of interest. The investigated sequence shows high homology to a regulatory site of nucleoporin 50, an element of the nuclear pore complex, and site specific cleavage of nucleoporin 50 was determined in vitro suggesting a novel link between the ionizing radiation-regulated proteasome and nuclear protein shuttling.

DOI : 10.1002/pmic.200900162 

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