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Title

Substrate screening identifies a novel target sequence for the proteasomal activity regulated by ionizing radiation

Authors
Broggini-Tenzer, Angela
Hollenstein, Andreas
Pianowski, Zbigniew
Wampfler, Andrea
Furmanova, Polina
Pruschy, Martin
Published in Proteomics. 2010, vol. 10, no. 2, p. 304-314
Abstract 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.
Keywords BiomedicineIonizing radiationNucleoporin 50Phage displayProteasome inhibitorSubstrate sequence
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Article (Published version) (334 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://doi.wiley.com/10.1002/pmic.200900162
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BROGGINI-TENZER, Angela et al. Substrate screening identifies a novel target sequence for the proteasomal activity regulated by ionizing radiation. In: Proteomics, 2010, vol. 10, n° 2, p. 304-314. https://archive-ouverte.unige.ch/unige:24701

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Deposited on : 2012-12-18

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