David Komander

..Our results highlight remarkable specificity determinants within the ubiquitin system...

..The conformational constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains, explaining why TAK1 cannot be activated by linear ubiquitination events...

..Reminiscent of a code, the various ubiquitin modifications adopt distinct conformations and lead to different outcomes in cells. Here, we discuss the structure, assembly, and function of this ubiquitin code...

..Due to their wide-ranging involvement in key regulatory processes, these enzymes might provide new therapeutic targets...

..For example, ubiquitination may have important allosteric roles in protein regulation that are currently not appreciated...

..The individual deubiquitinase families are discussed with a focus on structure, regulation and specificity features for selected enzymes...

..In this issue of Molecular Cell, Maurice and colleagues demonstrate that nondegradative Lys63-linked polyubiquitin chains modulate Dishevelled (Dvl) activity upstream in the Wnt/beta-catenin signaling pathway...

..Our data highlight the intrinsic specificity of the ubiquitin system that extends to Lys11-linked chains and emphasize that differentially linked polyubiquitin chains must be regarded as independent post-translational modifications...

..Our data are consistent with AnkUBD functioning as an enzymatic S1' ubiquitin-binding site, which orients a ubiquitin chain so that Lys29 and Lys33 linkages are cleaved preferentially...

..We also rationalize the inability of USP21 to target NEDD8 and identify differences that allow USPs to distinguish between structurally related modifications...

..ISGylation in viral infection. Furthermore, the crystal structures will allow structure-based design of antiviral agents targeting this enzyme...

..Our report illustrates that specificity in the interaction between autophagy receptors and autophagy machinery is of functional importance to execute selective autophagy...

..The importance of Lys11 linkages and Met1 linkages in cell cycle regulation and nuclear factor-κB activation, respectively, highlight that the different ubiquitin chain types should be considered as functionally independent PTMs...

..Notably, mechanistic insights have revealed how the E2 ubiquitin-conjugating enzyme UBE2S achieves its Lys11 linkage specificity, and two structures of Lys11-linked polyubiquitin highlight the dynamic nature of this compact chain type...

..Using chemical tools to detect sulphenic acid intermediates, we show that many ovarian tumour deubiquitinases undergo reversible oxidation upon treatment with H2O2, revealing a new mechanism to regulate deubiquitinase activity...

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..Here, we describe a method to synthesise K11-linked ubiquitin chains in vitro by exploiting the intrinsic K11-specificity of the E2 enzyme UBE2S...

..Moreover, we profile a panel containing 10% of the known human deubiquitinases on Lys6- and Lys29-linked ubiquitin and discover that TRABID cleaves the Lys29 linkage 40-fold more efficiently than the Lys63 linkage...

..These results provide new insights into the regulation of BIM(EL) by defining a novel ubiquitin-independent pathway for the proteasome-dependent destruction of this highly toxic protein...

..Yeast USP domains have a different pattern of inserted sequences, suggesting that the insertions are hotspots for evolutionary diversity to expand USP functionality...