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

Autor: Angela Broggini-Tenzer, Martin Pruschy, Zbigniew Pianowski, Andreas Hollenstein, Polina Furmanova, Nicolas Winssinger, Andrea Wampfler
Přispěvatelé: University of Zurich, Pruschy, M
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Proteomics, Vol. 10, No 2 (2010) pp. 304-314
ISSN: 1615-9853
DOI: 10.5167/uzh-32128
Popis: 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.
Databáze: OpenAIRE