Post-translational modification of proteins with ubiquitin (Ub) and Ub chains controls protein breakdown by the proteasome, cellular localization of proteins, transcriptional activity, and DNA repair. Ubiquitin is a highly conserved 76 amino acid protein that can be linked to target proteins through an isopeptide bond between the C-terminal carboxylate of Ub and the e-amine of a lysine residue ...

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 lysine (K) 48 residues. Differently linked polymers of polyubiquitin have been found that modify proteins without targeting to proteasomal degradation. Instead this...

to render proteolysis ATP dependent. The lid binds the base and is thought to render proteolysis dependent upon the prior synthesis of a multiubiquitin chain on a Rati Verma and Raymond J. Deshaies* Division of Biology, 156-29 California Institute of Technology substrate protein. Pasadena, California 91125 The covalent attachment of ubiquitin to acceptor lysines in a substrate (“ubiquitination”...

Conjugation of ubiquitin to target proteins is a finely tuned process involving a reaction, culminating in the conjugation of a single ubiquitin (1). The first step is conjugation of a single ubiquitin molecule to the substrate’s protein amino group (monoubiquitination) or to multiple amino groups (multimonoubiquitination), which can remain as it is or be further extended by additional ubiquiti...

Cells of the innate immune system, including dendritic cells (DCs) and macrophages, have an important role in regulating the nature and magnitude of adaptive immune responses1. They recognize microbial components via pattern-recognition receptors, including various Tolllike receptors (TLRs), which trigger intracellular signaling events that induce the maturation and function of these cells. DCs...

Eukaryotic cells are made more diverse and complex by an intricate ensemble of post-translational modifications to their proteins. Of these, ubiquitination is perhaps the most fateful. Ubiquitin (Ub) is a small, robust, highly conserved protein (Figure 1). The covalent attachment of ubiquitin marks cellular proteins for degradation by the proteasome, and can elicit other consequences as well. D...

Commentary on: Xiong Y, Wang L, Xu S, Fu B, Che Zaky MY, Tian R, Yao Guo D, Sha Z, Lin F, X, Wu H. Small molecule Z363 co-regulates TAF10 and MYC via the E3 ligase TRIP12 to suppress tumour growth. Clin Transl Med. 2023;13(1):e1153. doi: 10.1002/ctm2.1153 is a pleiotropic transcription factor involved in regulation of critical cellular processes including cell proliferation, differentiation apo...

Mitochondria are essential organelles that execute and coordinate various metabolic processes in the cell. Mitochondrial dysfunction severely affects cell fitness contributes to disease. Proper organellar function depends on biogenesis maintenance of mitochondria its >1,000 proteins. As a result, has evolved mechanisms protein quality control, such as turnover proteins via mitochondria-associat...

The translocation of sphingosine kinase 1 (SK1) to the plasma membrane (PM) is crucial in promoting oncogenesis. We have previously proposed that SK1 exists as both a monomer and dimer equilibrium, although it unclear whether these species translocate PM via same or different mechanisms. therefore investigated structural determinants involved better understand how might potentially be targeted ...