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 |
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Přispěvatelé: | University of Zurich, Pruschy, M |
Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Ionizing radiation
Proteomics Proteasome Endopeptidase Complex 1303 Biochemistry medicine.medical_treatment Clinical Biochemistry Down-Regulation Regulatory site 610 Medicine & health Biology Cleavage (embryo) Biochemistry Cell Line Substrate Specificity Mice Peptide Library Radiation Ionizing medicine 1312 Molecular Biology Animals Proteasome inhibitor Amino Acid Sequence Nuclear pore Nuclear protein Molecular Biology Protease 10044 Clinic for Radiation Oncology Up-Regulation Nuclear Pore Complex Proteins Biomedicine Nucleoporin 50 Proteasome Phage display Nucleoporin Substrate sequence medicine.drug |
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 |
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