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1. Formylation of Eukaryotic Cytoplasmic Proteins: Linking Stress to Degradation

Author:
Eldeeb, Mohamed A.; Fahlman, Richard P.; Esmaili, Mansoore; Fon, Edward A.
Source:
Trends in biochemical sciences 2019 v.44 no.3 pp. 181-183
ISSN:
0968-0004
Subject:
protein degradation,   etc   ; eukaryotic cells; methionine; mitochondria; prokaryotic cells; proteins;     Show all 6 Subjects
Abstract:
... Unlike prokaryotes, N-terminal formylation has been confined to a handful of mitochondrial proteins in eukaryotes. A recent study unveils a new role for eukaryotic cytoplasmic N-terminal formylation linking diverse cellular stresses to N-terminal-dependent protein degradation. These findings suggest broad cellular implications in higher eukaryotes for N-terminal methionine formylation. ...
DOI:
10.1016/j.tibs.2018.12.008

2. Structure of hRpn10 Bound to UBQLN2 UBL Illustrates Basis for Complementarity between Shuttle Factors and Substrates at the Proteasome

Author:
Chen, Xiang; Ebelle, Danielle L.; Wright, Brandon J.; Sridharan, Vinidhra; Hooper, Evan; Walters, Kylie J.
Source:
Journal of molecular biology 2019 v.431 no.5 pp. 939-955
ISSN:
0022-2836
Subject:
protein degradation,   etc   ; nuclear magnetic resonance spectroscopy; proteasome endopeptidase complex; titration; ubiquitin; ubiquitination;     Show all 6 Subjects
Abstract:
... The 26S proteasome is a highly complex 2.5-MDa molecular machine responsible for regulated protein degradation. Proteasome substrates are typically marked by ubiquitination for recognition at receptor sites contributed by Rpn1/S2/PSMD2, Rpn10/S5a, and Rpn13/Adrm1. Each receptor site can bind substrates directly by engaging conjugated ubiquitin chains or indirectly by binding to shuttle factors Rad ...
DOI:
10.1016/j.jmb.2019.01.021

3. The pivotal oncogenic role of Jab1/CSN5 and its therapeutic implications in human cancer

Author:
Guo, Zhen; Wang, Youhong; Zhao, Yu; Shu, Yan; Liu, Zhaoqian; Zhou, Honghao; Wang, Hui; Zhang, Wei
Source:
Gene 2019 v.687 pp. 219-227
ISSN:
0378-1119
Subject:
protein degradation,   etc   ; DNA repair; angiogenesis; apoptosis; cell cycle; humans; neoplasms; prognosis; signal transduction; therapeutics;     Show all 10 Subjects
Abstract:
... Jab1/CSN5 is a conserved multifunctional protein involved in ubiquitin-mediated protein degradation. Deregulation of Jab1/CSN5 can exert dramatic effects on diverse cellular functions, including DNA repair, cell cycle control, apoptosis, angiogenesis, and signal transduction, all of which are critical for tumor development. Although increasing evidence has demonstrated that Jab1/CSN5 was overexpre ...
DOI:
10.1016/j.gene.2018.11.061

4. VHL regulates NEK1 via both HIF-2α pathway and ubiquitin-proteasome pathway in renal cancer cell

Author:
Chen, Guang; Zhou, Jun; Chen, Jie; Zhu, Jin; Liu, Shuang-Chun; Ding, Xiao-Fei; Zhang, Qiang
Source:
Biochemical and biophysical research communications 2019 v.509 no.3 pp. 797-802
ISSN:
0006-291X
Subject:
protein degradation,   etc   ; enzymes; hypoxia; hypoxia-inducible factor 1; neoplasms; promoter regions; ubiquitination;     Show all 7 Subjects
Abstract:
... Both Von Hippel-Lindau tumor suppressor (VHL) and Never-in-mitosis A (NIMA)-related kinase 1 (NEK1) are involved in primary cilium formation, but whether VHL could regulate NEK1 is unknown. Here, we demonstrated that renal cancer cells Caki-1 and ACHN with wild-type VHL expressed lower level of NEK1 than that of VHL-defective cells including 786-O, 769-P and A498 cells. VHL-overexpression down-reg ...
DOI:
10.1016/j.bbrc.2019.01.001

5. Implications of Microglia in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Author:
Haukedal, Henriette; Freude, Kristine
Source:
Journal of molecular biology 2019
ISSN:
0022-2836
Subject:
protein degradation,   etc   ; amyotrophic lateral sclerosis; autophagy; central nervous system; dementia; genes; inflammation; mutation; neuroglia; neurons; pathogenesis;     Show all 11 Subjects
Abstract:
... Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with clear similarities regarding their clinical, genetic and pathological features. Both are progressive, lethal disorders, with no current curative treatment available. Several genes that correlated with ALS and FTD are implicated in the same molecular pathways. Strikingly, many of these genes a ...
DOI:
10.1016/j.jmb.2019.02.004

6. Toward the understanding of the role of CDC48, a major component of the protein quality control, in plant immunity

Author:
Bègue, Hervé; Mounier, Arnaud; Rosnoblet, Claire; Wendehenne, David
Source:
Plant science 2019 v.279 pp. 34-44
ISSN:
0168-9452
Subject:
protein degradation,   etc   ; animals; cell death; cell division; immune response; immunologic receptors; metabolism; pathogens; viral proteins; yeasts;     Show all 10 Subjects
Abstract:
... The evolutionally conserved chaperone-like protein CDC48 (cell division cycle 48) is a major component of ubiquitin-dependent protein degradation pathways in animal and yeast and, more generally, of the protein quality control machinery. In plants, CDC48 plays essential regulatory functions in development and the possibly that it contributes to protein degradation through the ubiquitin-proteasome ...
DOI:
10.1016/j.plantsci.2018.10.029

7. Proteasome-mediated protein degradation is enhanced by fusion ubiquitin with unstructured degron

Author:
Inobe, Tomonao; Tsukamoto, Masayuki; Nozaki, Miyuki
Source:
Biochemical and biophysical research communications 2018 v.501 no.4 pp. 948-954
ISSN:
0006-291X
Subject:
protein degradation,   etc   ; proteasome endopeptidase complex; ubiquitin;     Show all 3 Subjects
Abstract:
... Methods to induce proteasomal degradation of unwanted proteins are valuable in biomedical studies and thus receive increasing attention. For efficient degradation, the proteasome requires both a ubiquitin tag, which delivers substrates to the proteasome, and an unstructured region, where the proteasome engages the substrate for unfolding and degradation. We fused two degron components into a singl ...
DOI:
10.1016/j.bbrc.2018.05.088

8. Pro(moting) the Turnover of Gluconeogenic Enzymes by a New Branch of the N-end Rule Pathway

Author:
Dougan, David A.
Source:
Trends in biochemical sciences 2017 v.42 no.5 pp. 330-332
ISSN:
0968-0004
Subject:
protein degradation,   etc   ; enzymes; gluconeogenesis;     Show all 3 Subjects
Abstract:
... The N-end rule pathway is a set of protein degradation systems that link the in vivo stability of a protein to its N-terminal residue. A recent paper from Alexander Varshavsky’s laboratory [1] identifies a new branch of the N-end rule pathway that specifically recognizes the N-terminal Pro residue of key gluconeogenesis enzymes. ...
DOI:
10.1016/j.tibs.2017.03.006

9. Specific and Fuzzy Interactions Cooperate in Modulating Protein Half-Life

Author:
Sharma, Rashmi; Demény, Máté; Ambrus, Viktor; Király, Sándor Balázs; Kurtán, Tibor; Gatti-Lafranconi, Pietro; Fuxreiter, Monika
Source:
Journal of molecular biology 2019 v.431 no.8 pp. 1700-1707
ISSN:
0022-2836
Subject:
protein degradation,   etc   ; binding capacity; dimerization; half life; homeostasis; models; mutation; polypeptides; proteasome endopeptidase complex; protein metabolism; ubiquitin;     Show all 11 Subjects
Abstract:
... Protein degradation is critical for maintaining cellular homeostasis. The 20S proteasome is selective for unfolded, extended polypeptide chains without ubiquitin tags. Sequestration of such segments by protein partners, however, may provide a regulatory mechanism. Here we used the AP-1 complex to study how c-Fos turnover is controlled by interactions with c-Jun. We show that heterodimerization wit ...
DOI:
10.1016/j.jmb.2019.02.006

10. Stable isotope profiling for large‐scale evaluation of feed efficiency in Atlantic salmon (Salmo salar)

Author:
Dvergedal, Hanne; Ødegård, Jørgen; Mydland, Liv Torunn; Øverland, Margareth; Hansen, Jon Øvrum; Ånestad, Ragnhild Martinsen; Klemetsdal, Gunnar
Source:
Aquaculture research 2019 v.50 no.4 pp. 1153-1161
ISSN:
1355-557X
Subject:
protein degradation,   etc   ; Salmo salar; experimental diets; feed conversion; fish; liver; muscle tissues; muscles; nitrogen; protein metabolism; stable isotopes; weight gain;     Show all 12 Subjects
Abstract:
... In growing animals, individual variation in feed efficiency may arise from individual differences in growth rate and protein metabolism. Over a period of time, these factors will affect the ratio between ‘new’ vs. ‘old’ protein, which can be quantified using isotope profiling. The aim of this study was to investigate the relationship between relative weight gain and atom percentage excess ¹⁵N in t ...
DOI:
10.1111/are.13990

11. Highly efficient deproteinization with an ammonifying bacteria Lysinibacillus fusiformis isolated from brewery spent diatomite

Author:
Gong, Xiaoxi; Tian, Weijun; Bai, Jie; Qiao, Kaili; Zhao, Jing; Wang, Liang
Source:
Journal of bioscience and bioengineering 2019 v.127 no.3 pp. 326-332
ISSN:
1389-1723
Subject:
protein degradation,   etc   ; Lysinibacillus; ammonia; ammonium; bacteria; carbon; diatomaceous earth; free amino acids; glucose; inoculum; nitrogen; pH; rice protein; surface area;     Show all 14 Subjects
Abstract:
... To explore a new method for bio-regeneration of high-protein brewery spent diatomite, an ammonifying bacteria (BSD1) was screened out from it and identified as Lysinibacillus fusiformis. The protein degradation characteristics of BSD1 was studied with rice protein as the sole nitrogen source. Maximum protein degradation activity was obtained when BSD1 was inoculated with an inoculum of 5% into a m ...
DOI:
10.1016/j.jbiosc.2018.08.004

12. Physiological responses of eelgrass (Zostera marina) to ambient stresses such as herbicide, insufficient light, and high water temperature

Author:
Mochida, Kazuhiko; Hano, Takeshi; Onduka, Toshimitsu; Ito, Katsutoshi; Yoshida, Goro
Source:
Aquatic toxicology 2019 v.208 pp. 20-28
ISSN:
0166-445X
Subject:
protein degradation,   etc   ; Zostera marina; cell walls; energy; glutamine; growth retardation; herbicides; leucine; myo-inositol; photosynthesis; stress response; sucrose; water temperature;     Show all 13 Subjects
Abstract:
... This study aimed to elucidate the biological responses of eelgrass (Zostera marina) to artificially induced stresses such as herbicide (Irgarol 1051, Irg) exposure, insufficient light, and high water temperature (27 ± 1.0 °C) by evaluating growth inhibition, photosynthetic activity, and metabolomic profiles. After 14 days, all treatments inhibited growth, but photosynthetic activity was only reduc ...
DOI:
10.1016/j.aquatox.2018.12.018

13. Licoflavonol Reduces Aβ Secretion by Increasing BACE1 Phosphorylation to Facilitate BACE1 Degradation

Author:
Gu, Ming‐Yao; Chun, Yoon Sun; Yong, Ryu Shi; Yang, Hyun Ok
Source:
Molecular nutrition & food research 2019 v.63 no.3 pp. e1800474
ISSN:
1613-4125
Subject:
protein degradation,   etc   ; Glycyrrhiza uralensis; Western blotting; active ingredients; adenosine diphosphate; chloroquine; enzyme-linked immunosorbent assay; lysosomes; phosphorylation; proteins; secretion;     Show all 11 Subjects
Abstract:
... SCOPE: In the previous study, Glycyrrhiza uralensis Fisch extract (GUE) inhibited Aβ secretion by inhibiting β‐site APP‐cleaving enzyme 1 (BACE1) transcription, and the active compounds semilicoisoflavone B (SB) and licoflavonol (LF) inhibited Aβ secretion. SB corresponds to the same mechanism as GUE, but LF has a different mechanism. In this study, the mechanism underlying inhibition of Aβ by LF ...
DOI:
10.1002/mnfr.201800474

14. Bivalent Ligands for Protein Degradation in Drug Discovery

Author:
Scheepstra, Marcel; Hekking, Koen F.W.; van Hijfte, Luc; Folmer, Rutger H.A.
Source:
Computational and Structural Biotechnology Journal 2019 v.17 pp. 160-176
ISSN:
2001-0370
Subject:
protein degradation,   etc   ; biochemical pathways; biotechnology; chimerism; drugs; ligands; models; phosphotransferases (kinases); proteolysis; proteome; receptors; therapeutics; transcription factors; ubiquitin-protein ligase;     Show all 14 Subjects
Abstract:
... Targeting the “undruggable” proteome remains one of the big challenges in drug discovery. Recent innovations in the field of targeted protein degradation and manipulation of the ubiquitin-proteasome system open up new therapeutic approaches for disorders that cannot be targeted with conventional inhibitor paradigms. Proteolysis targeting chimeras (PROTACs) are bivalent ligands in which a compound ...
DOI:
10.1016/j.csbj.2019.01.006

15. The physiological role of the free 20S proteasome in protein degradation: A critical review

Author:
Demasi, Marilene; da Cunha, Fernanda Marques
Source:
Biochimica et biophysica acta 2018 v.1862 no.12 pp. 2948-2954
ISSN:
0304-4165
Subject:
protein degradation,   etc   ; oxidation; proteasome endopeptidase complex; proteins; proteolysis;     Show all 5 Subjects
Abstract:
... It has been almost three decades since the removal of oxidized proteins by the free 20S catalytic unit of the proteasome (20SPT) was proposed. Since then, experimental evidence suggesting a physiological role of proteolysis mediated by the free 20SPT has being gathered.Experimental data that favors the hypothesis of free 20SPT as playing a role in proteolysis are critically reviewed.Protein degrad ...
DOI:
10.1016/j.bbagen.2018.09.009

16. Targeting Metalloenzymes for Therapeutic Intervention

Author:
Chen, Allie Y.; Adamek, Rebecca N.; Dick, Benjamin L.; Credille, Cy V.; Morrison, Christine N.; Cohen, Seth M.
Source:
Chemical reviews 2018 v.119 no.2 pp. 1323-1455
ISSN:
1520-6890
Subject:
protein degradation,   etc   ; bioactive properties; drugs; landscapes; nucleic acids; therapeutics;     Show all 6 Subjects
Abstract:
... Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many others. The role of metalloenzymes in these processes also makes them central for the progression of many diseases and, as such, makes metalloenzymes attractive targets for therapeutic intervention. Increasing awareness of the role metalloenzymes play in ...
DOI:
10.1021/acs.chemrev.8b00201

17. Life and death of proteins after protease cleavage: protein degradation by the N‐end rule pathway

Author:
Dissmeyer, Nico; Rivas, Susana; Graciet, Emmanuelle
Source:
Thenew phytologist 2018 v.218 no.3 pp. 929-935
ISSN:
0028-646X
Subject:
protein degradation,   etc   ; cell proliferation; pathogens; proteinases; proteins; proteomics;     Show all 6 Subjects
Abstract:
... Contents Summary 929 I. Introduction: conservation and diversity of N‐end rule pathways 929 II. Defensive functions of the N‐end rule pathway in plants 930 III. Proteases and degradation by the N‐end rule pathway 930 IV. New proteomics approaches for the identification of N‐end rule substrates 932 V. Concluding remarks 932 Acknowledgements 934 References 934 SUMMARY: The N‐end rule relates the sta ...
DOI:
10.1111/nph.14619

18. Porcine teschovirus 2 induces an incomplete autophagic response in PK-15 cells

Author:
Gu, Yuanxing; Zhou, Yingshan; Shi, Xinfeng; Xin, Yongping; Shan, Ying; Chen, Cong; Cao, Tong; Fang, Weihuan; Li, Xiaoliang
Source:
Archives of virology 2018 v.163 no.3 pp. 623-632
ISSN:
0304-8608
Subject:
protein degradation,   etc   ; Porcine teschovirus; autophagy; pathogens; rapamycin; viruses;     Show all 6 Subjects
Abstract:
... Autophagy is a homeostatic process that has been shown to be vital in the innate immune defense against pathogens. However, little is known about the regulatory role of autophagy in porcine teschovirus 2 (PTV-2) replication. In this study, we found that PTV-2 infection induces a strong increase in GFP-LC3 punctae and endogenous LC3 lipidation. However, PTV-2 infection did not enhance autophagic pr ...
DOI:
10.1007/s00705-017-3652-2

19. Urinary phthalate metabolite concentrations in relation to levels of circulating matrix metalloproteinases in pregnant women

Author:
Bedrosian, Leah D.; Ferguson, Kelly K.; Cantonwine, David E.; McElrath, Thomas F.; Meeker, John D.
Source:
The Science of the total environment 2018 v.613-614 pp. 1349-1352
ISSN:
0048-9697
Subject:
protein degradation,   etc   ; humans; metabolites; metalloproteinases; phthalates; pregnancy outcome; pregnant women;     Show all 7 Subjects
Abstract:
... Phthalate exposure has been shown to be associated with adverse pregnancy outcomes. However, human studies informing relevant mechanistic pathways are lacking. Experimental studies have reported that matrix metalloproteinases (MMPs), which are responsible for extracellular protein degradation, may be upregulated in response to phthalate exposure. In this exploratory study we measured urinary phtha ...
DOI:
10.1016/j.scitotenv.2017.09.244

20. Substrate Sorting by a Supercharged Nanoreactor

Author:
Azuma, Yusuke; Bader, Daniel L. V.; Hilvert, Donald
Source:
Journal of the American Chemical Society 2018 v.140 no.3 pp. 860-863
ISSN:
1520-5126
Subject:
protein degradation,   etc   ; catalysts; encapsulation; polypeptides; proteinases; proteins; substrate specificity; zwitterions;     Show all 8 Subjects
Abstract:
... Compartmentalization of proteases enables spatially and temporally controlled protein degradation in cells. Here we show that an engineered lumazine synthase protein cage, which possesses a negatively supercharged lumen, can exploit electrostatic effects to sort substrates for an encapsulated protease. This proteasome-like nanoreactor preferentially cleaves positively charged polypeptides over bot ...
DOI:
10.1021/jacs.7b11210