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1. BacPROTACs mediate targeted protein degradation in bacteria

Author:
Francesca E. Morreale; Stefan Kleine; Julia Leodolter; Sabryna Junker; David M. Hoi; Stepan Ovchinnikov; Anastasia Okun; Juliane Kley; Robert Kurzbauer; Lukas Junk; Somraj Guha; David Podlesainski; Uli Kazmaier; Guido Boehmelt; Harald Weinstabl; Klaus Rumpel; Volker M. Schmiedel; Markus Hartl; David Haselbach; Anton Meinhart; Markus Kaiser; Tim Clausen
Source:
Cell 2022 v.185 no.13 pp. 2338-2353.e18
ISSN:
0092-8674
Subject:
protein degradation,   etc   ; antibiotics; proteinases;     Show all 3 Subjects
Abstract:
... Hijacking the cellular protein degradation system offers unique opportunities for drug discovery, as exemplified by proteolysis-targeting chimeras. Despite their great promise for medical chemistry, so far, it has not been possible to reprogram the bacterial degradation machinery to interfere with microbial infections. Here, we develop small-molecule degraders, so-called BacPROTACs, that bind to t ...
DOI:
10.1016/j.cell.2022.05.009

2. Target and tissue selectivity of PROTAC degraders

Author:
Robert G. Guenette; Seung Wook Yang; Jaeki Min; Baikang Pei; Patrick Ryan Potts
Source:
Chemical Society reviews 2022 v.51 no.14 pp. 5740-5756
ISSN:
1460-4744
Subject:
protein degradation,   etc   ; ligands; ligases; proteolysis;     Show all 4 Subjects
Abstract:
... Targeted protein degradation (TPD) strategies have revolutionized how scientists tackle challenging protein targets deemed undruggable with traditional small molecule inhibitors. Many promising campaigns to inhibit proteins have failed due to factors surrounding inhibition selectivity and targeting of compounds to specific tissues and cell types. One of the major improvements that PROTAC (proteoly ...
DOI:
10.1039/d2cs00200k

3. 3-Aminophthalic acid, a new cereblon ligand for targeted protein degradation by O’PROTAC

Author:
Yuqian Yan; Jingwei Shao; Donglin Ding; Yunqian Pan; Phuc Tran; Wei Yan; Zhengyu Wang; Hong-yu Li; Haojie Huang
Source:
Chemical communications 2022 v.58 no.14 pp. 2383-2386
ISSN:
1364-548X
Subject:
protein degradation,   etc   ; ligands; transcription factors; ubiquitin-protein ligase;     Show all 4 Subjects
Abstract:
... In this study, we identified 3-aminophthalic acid as a new ligand of cereblon (CRBN) E3 ubiquitin ligase and developed a phthalic acid-based O’PROTAC for degradation of the ERG transcription factor. This phthalic acid-based O’PROTAC presented an efficacy in degrading ERG comparable to those displayed by pomalidomide-based ERG O’PROTACs. Moreover, phthalic acid—being more chemically stable and econ ...
DOI:
10.1039/d1cc06525d

4. Targeting the deubiquitinase USP7 for degradation with PROTACs

Author:
Arunima Murgai; Izidor Sosič; Martina Gobec; Patricia Lemnitzer; Matic Proj; Sophie Wittenburg; Rabea Voget; Michael Gütschow; Jan Krönke; Christian Steinebach
Source:
Chemical communications 2022 v.58 no.63 pp. 8858-8861
ISSN:
1364-548X
Subject:
protein degradation,   etc   ; apoptosis; drugs; humans; ligands; proteinases; therapeutics;     Show all 7 Subjects
Abstract:
... Targeting deubiquitinating enzymes (DUBs) has emerged as a promising therapeutic approach in several human cancers and other diseases. DUB inhibitors are exciting pharmacological tools but often exhibit limited cellular potency. Here we report PROTACs based on a ubiquitin-specific protease 7 (USP7) inhibitor scaffold to degrade USP7. By investigating several linker and E3 ligand types, including n ...
DOI:
10.1039/d2cc02094g

5. Co-hydrothermal carbonization of rape straw and microalgae: pH-enhanced carbonization process to obtain clean hydrochar

Author:
Xiangmin Liu; Yuwei Fan; Yunbo Zhai; Xiaoping Liu; Zhexian Wang; Ya Zhu; Haoran Shi; Caiting Li; Yun Zhu
Source:
Energy 2022 v.257 pp. 124733
ISSN:
0360-5442
Subject:
protein degradation,   etc   ; carbonization; deamination; energy; hydrochars; microalgae; pH; straw;     Show all 8 Subjects
Abstract:
... In this study, co-hydrothermal carbonization of rape straw and microalgae was conducted for clean hydrochar. The effect of different feedwater pH values (pH = 1, 3, 5, 7, 9, 12) on co-HTC and the mechanism of enhanced N, S, and O removal were revealed. The acidic and alkaline environment of the feedwater exacerbates the carbonization process. The higher heating value (HHV) of the hydrochar formed ...
DOI:
10.1016/j.energy.2022.124733

6. Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications

Author:
Nathaniel J. Henning; Andrew G. Manford; Jessica N. Spradlin; Scott M. Brittain; Erika Zhang; Jeffrey M. McKenna; John A. Tallarico; Markus Schirle; Michael Rape; Daniel K. Nomura
Source:
Journal of the American Chemical Society 2022 v.144 no.2 pp. 701-708
ISSN:
1520-5126
Subject:
protein degradation,   etc   ; drugs; humans; ligands; therapeutics; ubiquitin-protein ligase;     Show all 6 Subjects
Abstract:
... Proteolysis-targeting chimeras (PROTACs), heterobifunctional compounds that consist of protein-targeting ligands linked to an E3 ligase recruiter, have arisen as a powerful therapeutic modality for targeted protein degradation (TPD). Despite the popularity of TPD approaches in drug discovery, only a small number of E3 ligase recruiters are available for the >600 E3 ligases that exist in human cell ...
DOI:
10.1021/jacs.1c03980

7. Protein degradation on the global scale

Author:
Emma V. Rusilowicz-Jones; Sylvie Urbé; Michael J. Clague
Source:
Molecular cell 2022 v.82 no.8 pp. 1414-1423
ISSN:
1097-2765
Subject:
protein degradation,   etc   ; cells; fields; gene editing; proteins; rating scales;     Show all 6 Subjects
Abstract:
... Protein degradation occurs through proteasomal, endosomal, and lysosomal pathways. Technological advancements have allowed for the determination of protein copy numbers and turnover rates on a global scale, which has provided an overview of trends and rules governing protein degradation. Sharper chemical and gene-editing tools have enabled the specific perturbation of each degradation pathway, who ...
DOI:
10.1016/j.molcel.2022.02.027

8. BRD2 interconnects with BRD3 to facilitate Pol II transcription initiation and elongation to prime promoters for cell differentiation

Author:
Chenlu Wang; Qiqin Xu; Xianhong Zhang; Daniel S. Day; Brian J. Abraham; Kehuan Lun; Liang Chen; Jie Huang; Xiong Ji
Source:
Cellular and molecular life sciences 2022 v.79 no.6 pp. 338
ISSN:
1420-682X
Subject:
protein degradation,   etc   ; cell differentiation; drugs; genomics; proteomics; transcription initiation;     Show all 6 Subjects
Abstract:
... The bromodomain and extraterminal motif (BET) proteins are critical drug targets for diseases. The precise functions and relationship of BRD2 with other BET proteins remain elusive mechanistically. Here, we used acute protein degradation and quantitative genomic and proteomic approaches to investigate the primary functions of BRD2 in transcription. We report that BRD2 is required for TAF3-mediated ...
DOI:
10.1007/s00018-022-04349-4

9. Fresh beef tumbling at different post‐mortem times to improve tenderness and proteolytic features of M. longissimus lumborum

Author:
Mariah J. Nondorf; Yuan H. Brad Kim
Source:
International journal of food science & technology 2022 v.57 no.5 pp. 3021-3030
ISSN:
0950-5423
Subject:
protein degradation,   etc   ; autolysis; beef; food science; longissimus muscle; proteolysis; technology;     Show all 7 Subjects
Abstract:
... The aim of this study was to determine the effects of tumbling at different post‐mortem times on the proteolytic features and quality attributes of beef loins (M. longissimus lumborum). Loins (n = 12) were cut into 4 sections and assigned to tumbling at 1, 6 or 11 days post‐mortem or non‐tumbled control. Upon tumbling, additional ageing was applied to a common post‐mortem time of 16 days. In gener ...
DOI:
10.1111/ijfs.15627

10. In vitro mannosidase activity of EDEM3 against asparagine-linked oligomannose-type glycans

Author:
Takashi Kikuma; Haruka Ibuki; Masaya Nakamoto; Akira Seko; Yukishige Ito; Yoichi Takeda
Source:
Biochemical and biophysical research communications 2022 v.612 pp. 44-49
ISSN:
0006-291X
Subject:
protein degradation,   etc   ; endoplasmic reticulum; glycoproteins; mannose; polysaccharides; quality control; research;     Show all 7 Subjects
Abstract:
... Oligomannose-type glycans on glycoproteins play an important role in the endoplasmic reticulum (ER)-protein quality control. Mannose trimming of the glycans triggers the ER-associated protein degradation pathway. In mammals, ER mannosyl-oligosaccharide 1,2-α-mannosidase 1 and three ER degradation -enhancing α-mannosidase-like proteins (EDEMs) are responsible for mannose trimming. However, the exac ...
DOI:
10.1016/j.bbrc.2022.04.094

11. Intrinsic and extrinsic regulators of Aux/IAA protein degradation dynamics

Author:
Marcelo Rodrigues Alves de Figueiredo; Lucia C. Strader
Source:
Trends in biochemical sciences 2022 v. no. pp. -
ISSN:
0968-0004
Subject:
protein degradation,   etc   ; acids; auxins; plant hormones; post-translational modification; proteins; transcription (genetics);     Show all 7 Subjects
Abstract:
... The plant hormone auxin acts through regulated degradation of Auxin/INDOLE-3-ACETIC ACID (Aux/IAA) proteins to regulate transcriptional events. In this review, we examine the composition and function of each Aux/IAA structural motif. We then focus on recent characterization of Aux/IAA N-terminal disordered regions, formation of secondary structure within these disordered regions, and post-translat ...
DOI:
10.1016/j.tibs.2022.06.004

12. The importance of cellular degradation kinetics for understanding mechanisms in targeted protein degradation

Author:
Kristin M. Riching; Elizabeth A. Caine; Marjeta Urh; Danette L. Daniels
Source:
Chemical Society reviews 2022 v.51 no.14 pp. 6210-6221
ISSN:
1460-4744
Subject:
protein degradation,   etc   ; phenotype; protein depletion; proteolysis; therapeutics; ubiquitin; ubiquitin-protein ligase; ubiquitination;     Show all 8 Subjects
Abstract:
... Targeted protein degradation has exploded over the past several years due to preclinical and early clinical therapeutic success of numerous compounds, and the emergence of new degradation modalities, which has broadened the definition of what a degrader is. The most characterized and well-studied small molecule degraders are molecular glues and proteolysis targeting chimeras (PROTACs). These degra ...
DOI:
10.1039/d2cs00339b

13. Pork longissimus dorsi marinated with edible mushroom powders: Evaluation of quality traits, microstructure, and protein degradation

Author:
Qingquan Fu; Haibo Shi; Dongxia Hu; Jingrong Cheng; Shoujiang Chen; Ailing Ben
Source:
Food research international 2022 v.158 pp. 111503
ISSN:
0963-9969
Subject:
protein degradation,   etc   ; Hypsizygus marmoreus; desmin; food research; longissimus muscle; marinating; microstructure; mushrooms; papain; pork;     Show all 10 Subjects
Abstract:
... In this study, we examined the effects of marination with five edible mushroom powders (3%, m/m) on the quality attributes and protein changes of pork longissimus dorsi compared to meat marinated with 0.2% papain and distilled water (control group). The results indicated that pork samples marinated with edible mushrooms displayed better water retention and lower shear force, especially in the 3% H ...
DOI:
10.1016/j.foodres.2022.111503

14. Sarcoplasmic and myofibril-bound calpains during storage of pork longissimus muscle: New insights on protein degradation

Author:
Jian Lyu; Per Ertbjerg
Source:
Food chemistry 2022 v.372 pp. 131347
ISSN:
0308-8146
Subject:
protein degradation,   etc   ; calcium; cold storage; desmin; food chemistry; longissimus muscle; myofibrils; pork; proteolysis; titration;     Show all 10 Subjects
Abstract:
... The subcellular distribution of calpain-1 and -2 and the proteolytical activity of myofibril-bound calpains in pork were investigated during 12 days cold storage. The content of sarcoplasmic calpain-1 decreased during storage while myofibril-bound calpain-1 content first increased (P < 0.05) to 17% of that of 12 h-sarcoplasmic calpain-1 on day 6 followed by a gradual decrease with subsequent stora ...
DOI:
10.1016/j.foodchem.2021.131347

15. CDC48B facilitates the intercellular trafficking of SHORT‐ROOT during radial patterning in roots

Author:
Lihui Yang; Mingyue Zhu; Yi Yang; Ke Wang; Yulei Che; Shurui Yang; Jinxiang Wang; Xin Yu; Lixin Li; Shuang Wu; Klaus Palme; Xugang Li
Source:
Journal of integrative plant biology 2022 v.64 no.4 pp. 843-858
ISSN:
1672-9072
Subject:
protein degradation,   etc   ; cell division; cortex; endodermis; fluorescence; genes; membrane fusion; mutants; root growth; stele;     Show all 10 Subjects
Abstract:
... CELL DIVISION CONTROL PROTEIN48 (CDC48) is essential for membrane fusion, protein degradation, and other cellular processes. Here, we revealed the crucial role of CDC48B in regulating periclinal cell division in roots by analyzing the recessive gen1 mutant. We identified the GEN1 gene through map‐based cloning and verified that GEN1 encodes CDC48B. gen1 showed severely inhibited root growth, incre ...
DOI:
10.1111/jipb.13231

16. Effects of chilling rate on progression of rigor mortis in postmortem lamb meat

Author:
Tongjing Yan; Chengli Hou; Zhenyu Wang; Xin Li; Li Chen; Ce Liang; Yujun Xu; Dequan Zhang
Source:
Food chemistry 2022 v.373 pp. 131463
ISSN:
0308-8146
Subject:
protein degradation,   etc   ; desmin; dissociation; food chemistry; lamb meat; myosin; rigor mortis; sarcomeres; troponin T;     Show all 9 Subjects
Abstract:
... This work investigated the effects of chilling rate on the progression of rigor mortis and explored possible mechanisms. Silverside from 18 lamb carcasses was assigned to control group (1.94 °C/h), very fast chilling-I group (VFC-I, 12.19 °C/h) and VFC-II group (15.10 °C/h). The shear force, myofibril fragmentation index (MFI), actomyosin ATPase activity, protein degradation and actomyosin dissoci ...
DOI:
10.1016/j.foodchem.2021.131463

17. Lactate dehydrogenase regulates basal glucose uptake in adipocytes

Author:
Tomomi Minemura; Atsunori Fukuhara; Michio Otsuki; Iichiro Shimomura
Source:
Biochemical and biophysical research communications 2022 v.607 pp. 20-27
ISSN:
0006-291X
Subject:
protein degradation,   etc   ; adipocytes; adipose tissue; blood glucose; glucose; glycolysis; lactate dehydrogenase; research; tissue weight;     Show all 9 Subjects
Abstract:
... Plasma glucose levels are homeostatically regulated within strict boundaries and are maintained through a balance between peripheral glucose uptake and hepatic glucose production. However, little is known about the regulatory mechanism of glucose uptake in adipocytes during fasting. Under fasting conditions, the expression levels of 8 glycolytic enzymes were significantly reduced in adipose tissue ...
DOI:
10.1016/j.bbrc.2022.03.113

18. Mechanisms underlying the deterioration of fish quality after harvest and methods of preservation

Author:
Xiaobao Nie; Ruichang Zhang; Lilin Cheng; Wenbo Zhu; Songlin Li; Xiaoming Chen
Source:
Food control 2022 v.135 pp. 108805
ISSN:
0956-7135
Subject:
protein degradation,   etc   ; enzyme activity; fish; food safety; lipid peroxidation; microbial contamination; shelf life; spoilage;     Show all 8 Subjects
Abstract:
... Lipid oxidation and/or protein decomposition caused by endogenous enzymatic activity and microbial contamination have a negative impact on the quality of fish in storage, increasing their perishability. Safe and effective alternative approaches for preserving fish quality and extending their shelf-life have been investigated more intensely over the recent decade, due to concerns about the safety o ...
DOI:
10.1016/j.foodcont.2021.108805

19. Melatonin delays leaf senescence and improves cucumber yield by modulating chlorophyll degradation and photoinhibition of PSII and PSI

Author:
Kun Liu; Tongtong Jing; Yanan Wang; Xizhen Ai; Huangai Bi
Source:
Environmental and experimental botany 2022 v.200 pp. 104915
ISSN:
0098-8472
Subject:
protein degradation,   etc   ; chlorophyll; chloroplasts; cucumbers; electron transfer; genes; greenhouses; leaves; melatonin; photoinhibition; photosystem II;     Show all 11 Subjects
Abstract:
... Decreases in chlorophyll and photosynthetic efficiency co-occur during aging and leaf senescence. Here, we report the positive functions of melatonin (MT) in delaying leaf senescence in cucumber plants. The results showed that natural leaf senescence induced the accumulation of endogenous MT and that spraying MT delayed leaf senescence in a concentration-dependent manner. Moreover, application of ...
DOI:
10.1016/j.envexpbot.2022.104915

20. Coral and it's symbionts responses to the typical global marine pollutant BaP by 4D-Proteomics approach

Author:
Yuebin Pei; Shuai Chen; Yuting Zhang; Volovych Olga; Yuanchao Li; Xiaoping Diao; Hailong Zhou
Source:
Environmental pollution 2022 v.307 pp. 119440
ISSN:
0269-7491
Subject:
protein degradation,   etc   ; Acropora; coral reefs; corals; microbiome; photosynthesis; pollutants; pollution; proteomics; stress response; symbiosis;     Show all 11 Subjects
Abstract:
... The symbiosis of corals, zooxanthellae, and microbes is the foundation of the coral reef ecosystem. In addition to global warming, marine pollutants are another important factor causing the breakdown of coral symbiosis. Benzo(a)pyrene (BaP) is a globally widespread marine environmental pollutant that poses a severe threat to marine ecosystems. However, responses of coral symbionts to global marine ...
DOI:
10.1016/j.envpol.2022.119440