A missing piece in the cell death and inflammation signaling pathway puzzle has been revealed
An international research team has discovered a previously unknown mechanism that plays a key role in the signaling pathways involved in programmed cell death. The team identified the protein HERC4 as an essential component of both TNF-induced necroptosis and apoptosis pathways—two processes that play a crucial role in maintaining cellular balance and triggering inflammatory responses.
An international team of researchers has uncovered a previously unknown mechanism that plays a crucial role in the cell death and inflammation signaling pathways, shedding light on the complex interactions between programmed cell death and inflammatory responses. The study, published in Nature Structural and Molecular Biology, identified the protein HERC4 as a key component in both TNF-induced necroptosis and apoptosis pathways.
Led by Dr. Sudan He from the Institute of Systems Medicine at Chinese Academy of Medical Sciences and Dr. Henning Walczak from the University of Cologne and UCL Cancer Institute, the research revealed that HERC4 acts as a critical switch in the TNF signaling pathway, regulating the transition from a survival signal to a death signal for cells.
By ubiquitinating kinase-active RIPK1, HERC4 initiates the formation of Complex II, which triggers cell death. This discovery not only explains the dual role of RIPK1 in both necroptosis and apoptosis but also highlights HERC4 as a promising therapeutic target for chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis.
The team's findings open up new possibilities for treating TNF-associated conditions, potentially leading to oral HERC4 inhibitors with broader therapeutic applications.
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