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

Broggini-Tenzer, Angela; Hollenstein, Andreas; Pianowski, Zbigniew; Wampfler, Andrea; Furmanova, Polina; Winssinger, Nicolas; Pruschy, Martin

doi:10.1002/pmic.200900162

Scientific article

English

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

Contributors

Broggini-Tenzer, Angela; Hollenstein, Andreas; Pianowski, Zbigniew; Wampfler, Andrea; Furmanova, Polina; Winssinger, Nicolas

; Pruschy, Martin

Published in

Proteomics, vol. 10, no. 2, p. 304-314

Publication date

2010

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

Biomedicine
Ionizing radiation
Nucleoporin 50
Phage display
Proteasome inhibitor
Substrate sequence

UNIGE affiliation entities

Not a UNIGE publication

Citation (ISO format)

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. doi: 10.1002/pmic.200900162

Article (Published version)

Identifiers

PID : unige:24701
DOI : 10.1002/pmic.200900162

Journal ISSN

1615-9853

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12/12/2012 09:59:00

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12/12/2012 09:59:00

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13/10/2025 23:52:49

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14/03/2023 17:47:44

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01/07/2026 06:09:46

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

Contributors

Published in

Publication date

Abstract

Keywords

UNIGE affiliation entities

Citation (ISO format)

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First validation

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Status update

Last indexation