RIP death domain structural interactions implicated in TNF-mediated proliferation and survival
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Updated: Aug 11, 2026

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
Published on: April 11, 2025
Juilee Thakar1, Karin Schleinkofer, Christoph Borner
1Department of Bioinformatics, Biocenter, Am Hubland, University of Wuerzburg, Wuerzburg, Germany.
Abstract:
Death domain (DD)-containing proteins are involved in both apoptosis and survival/proliferation signaling induced by activated death receptors. Here, a phylogenetic and structural analysis was performed to highlight differences in DD domains and their key regulatory interaction sites. The phylogenetic analysis shows that receptor DDs are more conserved than DDs in adaptors. Adaptor DDs can be subdivided into those that activate or inhibit apoptosis. Modeling of six homotypic DD interactions involved in the TNF signaling pathway implicates that the DD of RIP (Receptor interacting protein kinase 1) is capable of interacting with the DD of TRADD (TNFR1-associated death domain protein) in two different, exclusive ways: one that subsequently recruits CRADD (apoptosis/inflammation) and another that recruits NFkappaB (survival/proliferation).
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