Post-translational modification by ubiquitin (ubiquitination, ubiquitylation, ubiquitinylation) is used as a robust signaling mechanism in a variety of processes that are essential for cell homeostasis. Its signaling specificity is conferred by the inherent dynamics of ubiquitin, the multivalency of ubiquitin chains, and its subcellular context, often defined by ubiquitin receptors and the subs...

Three-dimensional H=C=N-NMR studies of yeast ubiquitin hydrolase (YUH1), substrate (ubiquitin) bound YUH1, and YUH1 bound ubiquitin, revealed the structural basis for the high specificity of YUH1 towards ubiquitin. The binding interface, defined by chemical shift perturbation of backbone resonances, included both ionic and hydrophobic stretches in YUH1 and ubiquitin. Based on the interaction su...

The ubiquitin-proteasome pathway fulfills major biological functions, but its physiologic tissue distribution and the interrelationship between pathway component activities and ubiquitin pools are unknown. Therefore, we analyzed free and conjugated ubiquitin, ubiquitin-protein ligation rates (UbPL) and chymotryptic- and tryptic-like proteasome peptidase activities in porcine skeletal muscle, he...

Ubiquitin phosphorylation is emerging as an important regulatory layer in the ubiquitin system. This is exemplified by the phosphorylation of ubiquitin on Ser65 by the Parkinson's disease-associated kinase PINK1, which mediates the activation of the E3 ligase Parkin. Additional phosphorylation sites on ubiquitin might also have important cellular roles. Here we report a versatile strategy for p...

Ubiquitin is a highly conserved 76 amino acid polypeptide, which is covalently attached to target proteins to signal their degradation by the 26S proteasome or to modify their function or localization. Regulated protein degradation, which is associated with many dynamic cellular processes, occurs predominantly via the ubiquitin-proteasome system. Ubiquitin is conjugated to target proteins throu...

Of all ubiquitin-like proteins, Rub1 (Nedd8 in mammals) is the closest kin of ubiquitin. We show via NMR that structurally, Rub1 and ubiquitin are fundamentally similar as well. Despite these profound similarities, the prevalence of Rub1/Nedd8 and of ubiquitin as modifiers of the proteome is starkly different, and their attachments to specific substrates perform different functions. Recently, s...

NDD: Neurodegenerative Disorders; ER: Endoplasmic Reticulum; UPS: Ubiquitin Proteasome System; ROS: Reactive Oxygen Species; AD: Alzheimer’s Disease; PD: Parkinson’s Disease; MS: Multiple Sclerosis; HD: Huntington’s Disease; ALS: Amyotrophic Lateral Sclerosis; PS: Presenilin; APP: Amyloid beta (A4) Precursor Protein; MARK1: Microtubule Affinity-Regulating Kinase 1; SOD-1: Superoxide Dismutase 1...