Universität zu Köln

Weiss, Konstantin ORCID: 0000-0003-4895-9459, Agarkova, Yelizaveta, Zwosta, Alexandra, Hoevel, Sarah, Himmelreich, Ann-Kathrin, Shumanska, Magdalena, Etich, Julia ORCID: 0000-0003-3238-6692, Poschmann, Gereon, Brachvogel, Bent ORCID: 0000-0002-3923-0554, Bogeski, Ivan ORCID: 0000-0001-9879-7174, Mielenz, Dirk and Riemer, Jan ORCID: 0000-0002-7574-8457 (2025). A fluorescent sensor for real-time monitoring of DPP8/9 reveals crucial roles in immunity and cancer. Life Science Alliance. pp. 1-19. EMBO Press. ISSN 2575-1077

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Abstract

[Artikel-Nr. e202403076] Dipeptidyl peptidases 8 and 9 (DPP8/9) are critical for the quality control of mitochondrial and endoplasmic reticulum protein import, immune regulation, cell adhesion, and cell migration. Dysregulation of DPP8/9 is associated with pathologies including tumorigenesis and inflammation. Commonly, DPP8/9 activity is analysed by in vitro assays using artificial substrates, which allow neither continuously monitoring DPP8/9 activity in individual, living cells nor detecting effects from endogenous interactors and posttranslational modifications. Here, we developed DiPAK (for DPP8/9 activity sensor based on AK2), a ratiometric genet- ically encoded fluorescent sensor, which enables studying DPP8/ 9 activity in living cells. Using DiPAK, we determined the dynamic range of DPP8/9 activity in cells overexpressing or lacking DPP9. We identified distinct activity levels among melanoma cell lines and found that LPS-induced primary B-cell activation depends on DPP8/9 as the absence of DPP8/9 activity results in apoptotic but not pyroptotic cell death. Consistently, we observed increasing DPP8/9 activity during B-cell maturation. Overall, DiPAK is a versatile tool for real-time single-cell monitoring of DPP8/9 activity in a broad range of cells and organisms

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Weiss, Konstantin UNSPECIFIED https://orcid.org/0000-0003-4895-9459 UNSPECIFIED Agarkova, Yelizaveta UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwosta, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoevel, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Himmelreich, Ann-Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Shumanska, Magdalena UNSPECIFIED UNSPECIFIED UNSPECIFIED Etich, Julia julia.etich@uni-koeln.de https://orcid.org/0000-0003-3238-6692 UNSPECIFIED Poschmann, Gereon UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED https://orcid.org/0000-0002-3923-0554 UNSPECIFIED Bogeski, Ivan UNSPECIFIED https://orcid.org/0000-0001-9879-7174 UNSPECIFIED Mielenz, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemer, Jan UNSPECIFIED https://orcid.org/0000-0002-7574-8457 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-798001
Identification Number:	10.26508/lsa.202403076
Journal or Publication Title:	Life Science Alliance
Page Range:	pp. 1-19
Date:	12 May 2025
Publisher:	EMBO Press
ISSN:	2575-1077
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin Zentrum für Molekulare Medizin
Subjects:	Chemistry and allied sciences Life sciences Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79800