XXXX 63 polyubiquitination in immunotherapy and in @entity5 .

@entity71112 @entity32 @entity1991 @entity19 @entity5 @entity71113 @entity376 @entity105 @entity792 @entity25433
Covalent and reversible post-translational modifications of proteins are a common theme in signaling. Ubiquitin conjugation was originally described to target proteins to proteasomal degradation by ubiquitin polymerization involving @entity376 (K) 48 residues. Differently linked polymers of polyubiquitin have been found that modify proteins without targeting to proteasomal degradation. Instead this pathway creates docking sites for signaling scaffolds that are key to control the @entity1991 ( @entity1991 ) pathway. Indeed @entity71112 , @entity25433 , and @entity71113 are E3 ubiquitin ligases that form K63-linked ubiquitin polymers. Therefore signaling via TNF family receptors, IL1R, IL-18R, T-cell receptor (TCR), and Toll-like receptors (TLR) use this type of post-translational modification. Specific enzymes exist (DUBs) that deactivate this system, degrading K63 polyubiquitin chains. Interestingly, @entity19 deficient in these deubiquitinases develop @entity792 and @entity32 . In @entity105 , the K63 polyubiquitin pathway is possibly critical for @entity5 . The pathway is also critically involved in costimulation of @entity5 immunity/immunotherapy as well as in the biology of malignant cells themselves. The elements of this new signaling paradigm offer the opportunity for therapeutic exploitation and drug discovery.
