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Article

Phosphocatalytic Kinome Activity Profiling of Apoptotic and Ferroptotic Agents in Multiple Myeloma Cells

1
Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
2
Department of Biomolecular Medicine, Ghent University, B-9000 Ghent, Belgium
*
Author to whom correspondence should be addressed.
Academic Editor: Sandra Marmiroli
Int. J. Mol. Sci. 2021, 22(23), 12731; https://doi.org/10.3390/ijms222312731
Received: 27 September 2021 / Revised: 16 November 2021 / Accepted: 22 November 2021 / Published: 25 November 2021
(This article belongs to the Special Issue Advances in Kinase Drug Discovery)
Through phosphorylation of their substrate proteins, protein kinases are crucial for transducing cellular signals and orchestrating biological processes, including cell death and survival. Recent studies have revealed that kinases are involved in ferroptosis, an iron-dependent mode of cell death associated with toxic lipid peroxidation. Given that ferroptosis is being explored as an alternative strategy to eliminate apoptosis-resistant tumor cells, further characterization of ferroptosis-dependent kinase changes might aid in identifying novel druggable targets for protein kinase inhibitors in the context of cancer treatment. To this end, we performed a phosphopeptidome based kinase activity profiling of glucocorticoid-resistant multiple myeloma cells treated with either the apoptosis inducer staurosporine (STS) or ferroptosis inducer RSL3 and compared their kinome activity signatures. Our data demonstrate that both cell death mechanisms inhibit the activity of kinases classified into the CMGC and AGC families, with STS showing a broader spectrum of serine/threonine kinase inhibition. In contrast, RSL3 targets a significant number of tyrosine kinases, including key players of the B-cell receptor signaling pathway. Remarkably, additional kinase profiling of the anti-cancer agent withaferin A revealed considerable overlap with ferroptosis and apoptosis kinome activity, explaining why withaferin A can induce mixed ferroptotic and apoptotic cell death features. Altogether, we show that apoptotic and ferroptotic cell death induce different kinase signaling changes and that kinome profiling might become a valid approach to identify cell death chemosensitization modalities of novel anti-cancer agents. View Full-Text
Keywords: ferroptosis; apoptosis; kinase; staurosporine; multiple myeloma; withaferin A ferroptosis; apoptosis; kinase; staurosporine; multiple myeloma; withaferin A
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MDPI and ACS Style

Logie, E.; Novo, C.P.; Driesen, A.; Van Vlierberghe, P.; Vanden Berghe, W. Phosphocatalytic Kinome Activity Profiling of Apoptotic and Ferroptotic Agents in Multiple Myeloma Cells. Int. J. Mol. Sci. 2021, 22, 12731. https://doi.org/10.3390/ijms222312731

AMA Style

Logie E, Novo CP, Driesen A, Van Vlierberghe P, Vanden Berghe W. Phosphocatalytic Kinome Activity Profiling of Apoptotic and Ferroptotic Agents in Multiple Myeloma Cells. International Journal of Molecular Sciences. 2021; 22(23):12731. https://doi.org/10.3390/ijms222312731

Chicago/Turabian Style

Logie, Emilie, Claudina P. Novo, Amber Driesen, Pieter Van Vlierberghe, and Wim Vanden Berghe. 2021. "Phosphocatalytic Kinome Activity Profiling of Apoptotic and Ferroptotic Agents in Multiple Myeloma Cells" International Journal of Molecular Sciences 22, no. 23: 12731. https://doi.org/10.3390/ijms222312731

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