| Autor: |
Anderson Daniel Ramos, Ying Yu Liang, Olga Surova, Smaranda Bacanu, Marc-Antoine Gerault, Tamoghna Mandal, Sophia Ceder, Anette Langebäck, Albin Österroos, George A. Ward, Jonas Bergh, Klas G. Wiman, Sören Lehmann, Nayana Prabhu, Sara Lööf, Pär Nordlund |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 43, Iss 10, Pp 114784- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114784 |
| Popis: |
Summary: Cellular phenotypes of apoptosis, as well as the activation of apoptosis caspase cascades, are well described. However, sequences and locations of early biochemical effector events after apoptosis initiation are still only partly understood. Here, we use integrated modulation of protein interaction states-cellular thermal shift assay (IMPRINTS-CETSA) to dissect the cellular biochemistry of early stages of apoptosis at the systems level. Using 5 families of cancer drugs and a new CETSA-based method to monitor the cleavage of caspase targets, we discover the initial biochemistry of the effector stage of apoptosis for all the studied drugs being focused on the peripheral nuclear region rather than the cytosol. Despite very different candidate apoptosis-inducing mechanisms of the drug families, as revealed by the CETSA data, they converge into related biochemical modulations in the peripheral nuclear region. This implies a higher control of the localization of the caspase cascades than previously anticipated and highlights the nuclear periphery as a critical vulnerability for cancer therapies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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