New ways of how necroptotic cell death is regulated in tumor cells
Necroptosis is a major form of programmed cell death capable of killing tumor cells resistant to common chemotherapy. Interestingly, necroptosis also plays central roles in other diseases, including infections and neurodegeneration. During necroptosis, the protein MLKL translocates to the cellular plasma membrane to create pores that quickly lead to cell death. The research group around PD Dr. rer. nat. Sjoerd van Wijk, group leader at the Institute of Experimental Pediatric Hematology and Oncology (Goethe-University Frankfurt and Frankfurter Stiftung for krebskranke Kinder) has now identified a new way of how MLKL membrane permeabilization and cell death is regulated. In collaboration with the laboratories of Prof. Dr. Melanie Boerries (University of Freiburg) and Dr. Francesco Pampaloni (Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt), as well as GenXpro GmbH (Frankfurt am Main), the group of van Wijk shows that the linear ubiquitin-specific E3 ligase LUBAC complex controls MLKL-mediated necroptosis and associated inflammatory signaling (https://www.nature.com/articles/s41419-024-06447-6). These new findings provide valuable insights in the molecular mechanisms of necroptosis, with important implications to overcome chemotherapy-resistant tumors.
Contact:
PD Dr. rer. nat. Sjoerd J. L. van Wijk, PhD
Institute of Experimental Pediatric Hematology and Oncology
Phone: 069 67866576
E-Mail: s.wijk@kinderkrebsstiftung-frankfurt.de
Image:
Immunofluorescence of membrane accumulation of active MLKL (green) in necroptotic cells (left) and necroptotic cells in which the LUBAC complex is inhibited (right). Cell nuclei are colored blue. (Image credit: Dr. rer. nat. Nadine Weinelt (Research group van Wijk)).
