...Kenrick A. Waite; Jeroen Roelofs ABSTRACT In the yeast Saccharomyces cerevisiae , proteasomes are enriched in cell nuclei, in which they execute important cellular functions. Nutrient stress can change this localization, indicating that proteasomes respond to the metabolic state of the cell...

..., which are themselves excluded from the final product. This is the case for the proteasome, a ubiquitous and highly conserved cellular regulator that mediates most selective intracellular protein degradation in eukaryotes. The proteasome consists of two subcomplexes: the core particle (CP), where...

...Jianhui Li; Mark Hochstrasser ABSTRACT The proteasome is central to proteolysis by the ubiquitin-proteasome system under normal growth conditions but is itself degraded through macroautophagy under nutrient stress. A recently described AMP-activated protein kinase (AMPK)-regulated endosomal sorting...

... demonstrated to be dependent on the proteasome. We show that BBS1 regulates this process by coupling the 19S proteasome regulatory subunit to the microtubule motor dynein for its transport to the centrosome. Our data identify the ciliopathy-related protein BBS1 as a new player in T cell synapse assembly...

... to a variety of protein aggregation disorders broadly termed proteinopathies. The AAA-ATPase p97 (also known as VCP), in combination with adaptor proteins, functions to identify ubiquitylated proteins and target them for degradation by the proteasome or through autophagy. Mutations in p97 cause multi-system...

...Didier Fesquet; David Llères; Charlotte Grimaud; Cristina Viganò; Francisca Méchali; Séverine Boulon; Olivier Coux; Catherine Bonne-Andrea; Véronique Baldin ABSTRACT PA28γ (also known as PSME3), a nuclear activator of the 20S proteasome, is involved in the degradation of several proteins regulating...

...Richard S. Marshall; David C. Gemperline; Fionn McLoughlin; Adam J. Book; Kay Hofmann; Richard D. Vierstra ABSTRACT The core protease (CP) subcomplex of the 26S proteasome houses the proteolytic active sites and assumes a barrel shape comprised of four co-axially stacked heptameric rings formed...

... proteasome. This poses the question as to why two ULMs sharing the proteasome-targeting function have evolved and how they differ from each other. This Review summarizes the current knowledge of the special structure of FAT10 and highlights its differences from ubiquitin. We discuss how these differences...

... to substrate proteins and serves as a signal for their rapid and irreversible degradation by the 26S proteasome similar to, yet independently of ubiquitin, thereby contributing to antigen presentation. Here, we have investigated whether FAT10 is involved in the formation and turnover of DALIS, and whether...

...-43-associated neurotoxicity. We demonstrate that Tnks-1/2 interacts with TDP-43 via a newly defined tankyrase-binding domain. Upon investigating the functional effect, we find that interaction with Tnks-1/2 inhibits the ubiquitination and proteasomal turnover of TDP-43, leading to its stabilization...

...Lauren Budenholzer; Carolyn Breckel; Christopher M. Hickey; Mark Hochstrasser ABSTRACT The proteasome is an essential regulator of protein homeostasis. In yeast and many mammalian cells, proteasomes strongly concentrate in the nucleus. Sts1 from the yeast Saccharomyces cerevisiae is an essential...

..., a condensin II inhibitor. Soluble small and other nuclear localization sequence (NLS)-targeted proteins then swiftly enter the expanding nuclear space. We then examined proteasomes, which are located in the cytoplasm and nucleus. A significant fraction of 20S proteasomes is imported by the importin IPO5...

.... Overexpression of GRWD1 decreased RPL23 protein levels and stability; this effect was restored upon treatment with the proteasome inhibitor MG132. EDD (also known as UBR5), an E3 ubiquitin ligase that interacts with GRWD1, also downregulated RPL23, and the decrease was further enhanced by co-expression of GRWD1...

... in a cell model of ALS induced by expressing mutant SOD1 (SOD1 A4V ). By monitoring the distribution of Ub in cells expressing SOD1 A4V , we show that Ub is present at the earliest stages of SOD1 A4V aggregation, and that cells containing SOD1 A4V aggregates have greater ubiquitin-proteasome system (UPS...

...-ubiquitinated) proteins and failures in proteasome-dependent degradation. Whereas the distribution of proteasomes and its role in synaptic function have been studied, whether proteasome activity regulates the axonal transport and metabolism of the amyloid precursor protein (APP), remains elusive. By using live...

...Ganapathi Kandasamy; Claes Andréasson ABSTRACT During protein quality control, proteotoxic misfolded proteins are recognized by molecular chaperones, ubiquitylated by dedicated quality control ligases and delivered to the 26S proteasome for degradation. Proteins belonging to the Hsp70 chaperone...

...Yandong Lai; Jin Li; Xiuying Li; Chunbin Zou ABSTRACT E3 ubiquitin ligase recognizes its protein substrates via specific molecular signatures for ubiquitin proteasomal degradation. However, the role of acetylation/deacetylation in the process of E3 ubiquitin ligase recognizing its protein...

... retrograde trafficking induced by proteasome inhibition. Mechanistically, this disrupted motility results from aberrant degradation of Miro2, a mitochondrial GTPase that links mitochondria to microtubules. Rescue experiments demonstrate that this Miro2 degradation involves the KEAP1–cullin-3 E3 ubiquitin...

...Tabita Kreko-Pierce; Benjamin A. Eaton ABSTRACT Because of their functional polarity and elongated morphologies, microtubule-based transport of proteins and organelles is critical for normal neuronal function. The proteasome is required throughout the neuron for the highly regulated degradation...

... by the DNA damage response pathway. Significantly, serpinB2 bound to and stabilized p21 to mediate senescence in a proteasome-independent manner, indicating that serpinB2 has a direct role in senescence. Thus, this study reveals a unique mechanism by which serpinB2 maintains senescence through stabilization...