Dynamic transcription of ubiquitin genes under basal and stressful conditions and new insights into the multiple UBC transcript variants

Bianchi, Marzia; Giacomini, Elisa; Crinelli, Rita; Radici, Lucia; Carloni, Elisa; Magnani, Mauro

doi:10.1016/j.gene.2015.07.030

Cited by 46 publications

(47 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conjugate increase was accompanied by a modest depletion of activated Ub and a twofold decrease in free Ub, presumably due to impaired proteasome-dependent recycling of Ub from conjugates. Different from this result, proteasome-inhibited MEF cells exhibited little change in free Ub levels, even though conjugated Ub increased 50%; instead, the total amount of Ub increased, likely due to increased expression of Ub genes 40 .…”

Section: Ub Pool Quantitation In Cell Lysatescontrasting

confidence: 76%

High-affinity free ubiquitin sensors as quantitative probes of ubiquitin homeostasis and deubiquitination

Choi

Bollinger

Prada

et al. 2019

Preprint

View full text Add to dashboard Cite

Ubiquitin (Ub) conjugation is an essential post-translational modification that affects nearly all proteins in eukaryotes. The functions and mechanisms of ubiquitination are areas of extensive and ongoing study, and yet the dynamics and regulation of even free (i.e., unconjugated) Ub are poorly understood. A major impediment has been the lack of simple and robust techniques to quantify Ub levels in cells and to monitor Ub release from conjugates. Here we describe the development of avidity-based fluorescent sensors that address this need. The sensors bind specifically to free Ub, have K d values down to 60 pM, and, in concert with a newly developed workflow, allow us to distinguish and quantify the pools of free, protein-conjugated, and thioesterified forms of Ub from cell lysates. Alternatively, free Ub in fixed cells can be visualized microscopically by staining with a sensor. Real-time assays using the sensors afford unprecedented flexibility and precision to measure deubiquitination of virtually any (poly)Ub conjugate.

show abstract

Section: Ub Pool Quantitation In Cell Lysatescontrasting

confidence: 76%

High-affinity free ubiquitin sensors as quantitative probes of ubiquitin homeostasis and deubiquitination

Choi

Bollinger

Prada

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The initial event which tags the misfolded proteins for subsequent degradation by UPS or CMA or autophagy is the poly‐ubiquitination. The ubiquitin precursor proteins in human are encoded by Ubb , Ubc, UBA52, and RPS27A genes and Ubb and Ubc, are shown to be upregulated by oxidative and proteotoxic stresses (Bianchi et al , ). We show that TRIM16 via NRF2 play a significant role in their upregulation.…”

Section: Discussionmentioning

confidence: 99%

TRIM16 controls assembly and degradation of protein aggregates by modulating the p62‐NRF2 axis and autophagy

et al. 2018

View full text Add to dashboard Cite

Sequestration of protein aggregates in inclusion bodies and their subsequent degradation prevents proteostasis imbalance, cytotoxicity, and proteinopathies. The underlying molecular mechanisms controlling the turnover of protein aggregates are mostly uncharacterized. Herein, we show that a TRIM family protein, TRIM16, governs the process of stress‐induced biogenesis and degradation of protein aggregates. TRIM16 facilitates protein aggregate formation by positively regulating the p62‐NRF2 axis. We show that TRIM16 is an integral part of the p62‐KEAP1‐NRF2 complex and utilizes multiple mechanisms for stabilizing NRF2. Under oxidative and proteotoxic stress conditions, TRIM16 activates ubiquitin pathway genes and p62 via NRF2, leading to ubiquitination of misfolded proteins and formation of protein aggregates. We further show that TRIM16 acts as a scaffold protein and, by interacting with p62, ULK1, ATG16L1, and LC3B, facilitates autophagic degradation of protein aggregates. Thus, TRIM16 streamlines the process of stress‐induced aggregate clearance and protects cells against oxidative/proteotoxic stress‐induced toxicity in vitro and in vivo. Taken together, this work identifies a new mechanism of protein aggregate turnover, which could be relevant in protein aggregation‐associated diseases such as neurodegeneration.

show abstract

“…Thus it stressed the importance of protein quality control which involved both UCHL1 and polyubiquitin precursor. Moreover UBC demonstrates a tissue-specific manner in coping with various cellular stresses instead of a generalized response[72, 80]. UBC is shown to be positively regulated by Sp1, MEK1 and FOXO3a in rat L6 muscle cell[80–82], and FOXO3a is neuroprotective in models of motoneuron diseases[83].…”

Section: Discussionmentioning

confidence: 99%

The essential and downstream common proteins of amyotrophic lateral sclerosis: A protein-protein interaction network analysis

et al. 2017

View full text Add to dashboard Cite

Amyotrophic Lateral Sclerosis (ALS) is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia (FTD) further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD (classical ALS + ALS/FTD) groups. The results suggest that classical ALS and ALS+FTD share similar essential protein set (VCP, FUS, TDP-43 and hnRNPA1) but have distinctive functional enrichment profiles. Thus, disruptions to these essential proteins might cause motoneuron susceptible to cellular stresses and eventually vulnerable to proteinopathies. Moreover, we identified a common downstream protein, ubiquitin-C, extensively interconnected with ALS-causative proteins (22 out of 24) which was not linked to ALS previously. Our in silico approach provides the computational background for identifying ALS therapeutic targets, and points out the potential downstream common ground of ALS-causative mutations.

show abstract

Dynamic transcription of ubiquitin genes under basal and stressful conditions and new insights into the multiple UBC transcript variants

Cited by 46 publications

References 46 publications

High-affinity free ubiquitin sensors as quantitative probes of ubiquitin homeostasis and deubiquitination

High-affinity free ubiquitin sensors as quantitative probes of ubiquitin homeostasis and deubiquitination

TRIM16 controls assembly and degradation of protein aggregates by modulating the p62‐NRF2 axis and autophagy

The essential and downstream common proteins of amyotrophic lateral sclerosis: A protein-protein interaction network analysis

Contact Info

Product

Resources

About