Cutting without cleaving: How caspase-1 shapes leukemia beyond enzymatic activity

Lukas M Braun; Robert Zeiser

doi:10.1016/j.chembiol.2025.12.011

Cutting without cleaving: How caspase-1 shapes leukemia beyond enzymatic activity

Cell Chem Biol. 2026 Jan 15;33(1):1-3. doi: 10.1016/j.chembiol.2025.12.011.

Authors

Lukas M Braun¹, Robert Zeiser²

Affiliations

¹ Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, a partnership between DKFZ and Medical Center - University of Freiburg, Freiburg, Germany.
² Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, a partnership between DKFZ and Medical Center - University of Freiburg, Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany. Electronic address: robert.zeiser@uniklinik-freiburg.de.

PMID: 41544612
DOI: 10.1016/j.chembiol.2025.12.011

Abstract

In this issue of Cell Chemical Biology, Uible et al.¹ uncover a previously unknown non-proteolytic role for caspase-1 (CASP1) in leukemia. CASP1 sustains leukemic growth by coordinating mTORC1-NF-κB signaling as scaffold for RPTOR, rather than regulating IL-1β and pyroptosis. CASP1's scaffolding function was found as a therapeutic vulnerability in leukemia.

MeSH terms

Animals
Caspase 1* / metabolism
Humans
Leukemia* / metabolism
Leukemia* / pathology
Mechanistic Target of Rapamycin Complex 1 / metabolism
NF-kappa B / metabolism
Signal Transduction

Substances

Caspase 1
Mechanistic Target of Rapamycin Complex 1
NF-kappa B