RIP death domain structural interactions implicated in TNF-mediated proliferation and survival.
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).
Thakar
Juilee
J
Department of Bioinformatics, Biocenter, Am Hubland, University of Wuerzburg, Wuerzburg, Germany.
Schleinkofer
Karin
K
Borner
Christoph
C
Dandekar
Thomas
T
D000595:Amino Acid Sequence; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D047888:Receptors, Tumor Necrosis Factor, Type I; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases