Review
Biochemistry & Molecular Biology
Qiyin Zhou, Yawen Zheng, Yi Sun
Summary: This review highlights the importance of mitochondria as the powerhouse of a cell, regulated by multiple signaling pathways. Post-translational modification like neddylation plays a crucial role in cellular metabolism and is involved in regulating the morphology, trafficking, and function of mitochondria. Understanding the mechanisms of how neddylation modulates mitochondria will advance our knowledge in mitochondrial regulation.
CELL AND BIOSCIENCE
(2021)
Review
Immunology
Xiaoying Zhang, Yu'e Liu, Tong Zhang, Yuying Tan, Xiangpeng Dai, Yong-Guang Yang, Xiaoling Zhang
Summary: Cullin-RING ligases (CRLs) are crucial regulators of the stability and activity of proteins related to the development of autoimmune diseases (AIDs), which involve complex signaling pathways. Understanding the underlying regulatory mechanisms of AIDs is important for developing effective therapeutic strategies. CRLs play critical roles in regulating AIDs through key inflammation-associated pathways and targeting them may lead to novel therapeutic approaches.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tiantian Xu, Qisheng Ma, Yanan Li, Qing Yu, Peichen Pan, Yawen Zheng, Zhijian Li, Xiufang Xiong, Tingjun Hou, Bin Yu, Hongmin Liu, Yi Sun
Summary: A small molecule called HA-9104 was discovered that effectively targets the UBE2F-CRL5 axis with independent anti-cancer activity or in combination with radiation. It binds to UBE2F, reduces its protein levels, inhibits cullin-5 neddylation, inactivates CRL5 activity, induces apoptosis, and induces DNA damage and G2/M arrest through the formation of DNA adducts.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Yeong-Mu Kim, Hye-Ji Kim, Dong-Kyu Kim, Dong-Hyun Jung, Hyo Je Cho, Sangjune Kim, Jihoon Nah, Sang-Min Jang
Summary: Cullin-RING E3 ubiquitin ligases spatially and temporally regulate the degradation of cellular proteins, and the speed of this regulation depends on the binding strength between each CUL and CSN5. The NAE inhibitor can rapidly inhibit NEDD8ylation in most CULs, while the deneddylation of CUL2 is slower.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Stephanie Diaz, Kankan Wang, Benita Sjogren, Xing Liu
Summary: Maintenance of protein homeostasis is crucial for eukaryotic biology, and the ubiquitin-proteasome system (UPS) plays an important role in the pathogenesis of cardiovascular diseases. Recent research has found that cullin-RING ubiquitin ligases (CRLs), an essential component of UPS, have significant physiological and pathological functions in the cardiovascular system.
Article
Multidisciplinary Sciences
Qiyin Zhou, Wenyu Lin, Chaoqun Wang, Fei Sun, Siwei Ju, Qian Chen, Yi Wang, Yongxia Chen, Haomin Li, Linbo Wang, Zeping Hu, Hongchuan Jin, Xian Wang, Yi Sun
Summary: This study reveals that neddylation inhibition increases glutamine metabolism by stabilizing glutamine transporter ASCT2, suggesting that targeting ASCT2 improves the anti-cancer effect of neddylation inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lukas T. Henneberg, Jaspal Singh, David M. Duda, Kheewoong Baek, David Yanishevski, Peter J. Murray, Matthias Mann, Sachdev S. Sidhu, Brenda A. Schulman
Summary: Researchers have developed conformation-specific antibodies to probe the NEDD8-activated cullin-RING ubiquitin E3 ligase networks in mammalian cells in response to extracellular stimuli, metabolic signals, and degrader drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Oncology
Jingrong Xian, Shiwen Wang, Yanyu Jiang, Lihui Li, Lili Cai, Ping Chen, Yue Liu, Xiaofei Zeng, Guoan Chen, Chen Ding, Robert M. Hoffman, Lijun Jia, Hu Zhao, Yanmei Zhang
Summary: This study found that NEDD8 is upregulated in ESCC and is associated with poorer patient survival. Downregulation of NEDD8 suppresses tumor growth and induces cell cycle arrest, DNA damage, and apoptosis in ESCC. The mechanism involves the accumulation of CRLs substrates, which can be attenuated by knockdown of DR5.
CANCER BIOLOGY & MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Yifan Chen, Xuejing Shao, Ji Cao, Hong Zhu, Bo Yang, Qiaojun He, Meidan Ying
Summary: The crosstalk between phosphorylation and ubiquitination plays a crucial role in tumorigenesis, providing new directions and strategies for tumor therapy.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Pharmacology & Pharmacy
Qianqian Song, Siqi Feng, Wenjun Peng, Anqi Li, Ting Ma, Bin Yu, Hong-Min Liu
Summary: Gastric carcinoma poses a serious threat to human health with high morbidity and mortality rates. The ubiquitination modification, specifically involving CRLs, plays a crucial role in the pathogenesis of gastric carcinoma by regulating various cellular pathways. Targeting a certain CULs member neddylation may be a promising strategy for selectively controlling cellular protein levels in cancer treatment.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Biotechnology & Applied Microbiology
Iqra Bano, Moolchand Malhi, Min Zhao, Liviu Giurgiulescu, Hira Sajjad, Marek Kieliszek
Summary: Cullin-RING E3 ligases (CRLs) are crucial components of the E3 ubiquitin ligase family, playing essential roles in various diseases, especially in tumor development, with neddylation being identified as an enticing target for anticancer drug discovery. Recent studies have shown significant advancements in protein neddylation, including preclinical and clinical target validation, in the search for neddylation inhibitor compounds.
Review
Oncology
Wenqi Du, Ruicheng Zhang, Bilal Muhammad, Dongsheng Pei
Summary: The COP9 signalosome (CSN) is a protein complex composed of 8 subunits that play crucial roles in cell proliferation, tumorigenesis, and DNA damage repair. CSN acts as a regulator at the intersection between neddylation and ubiquitination in cancer progression. Individual CSN subunits have potential as therapeutic targets for cancer therapy through regulation of transcription factors and the cell cycle.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Cell Biology
Shizhen Zhang, Xiahong You, Tiantian Xu, Qian Chen, Hua Li, Longyu Dou, Yilun Sun, Xiufang Xiong, Morgan A. Meredith, Yi Sun
Summary: In this study, it was found that MLN4924 increased the levels of PD-L1 mRNA and protein, which was largely independent of neddylation inactivation. The mechanism involved the activation of ERK and JNK signals, leading to AP-1 activation. MLN4924 attenuated T cell killing and this effect could be abrogated by MEK inhibitor or anti-PD-L1 antibody. Combination of MLN4924 with MEK inhibitor or anti-PD-L1 antibody enhanced the suppression of tumor growth in an in vivo xenograft tumor model.
CELL DEATH & DISEASE
(2022)
Article
Plant Sciences
Changhyun Choi, Jong Hee Im, Jinjeong Lee, Soon Il Kwon, Woe-Yeon Kim, Sang Ryeol Park, Duk-Ju Hwang
Summary: This study shows that OsDWD1 in rice suppresses immune responses by degrading OsNPR1. OsDWD1 acts as a negative regulator of the immune response, and OsNPR1 is its substrate. The CUL4-based E3 ligase system also influences OsNPR1 protein levels in Arabidopsis.
Article
Cell Biology
Sara Petillo, Cristina Capuano, Rosa Molfetta, Cinzia Fionda, Abdelilah Mekhloufi, Chiara Pighi, Fabrizio Antonangeli, Alessandra Zingoni, Alessandra Soriani, Maria Teresa Petrucci, Ricciarda Galandrini, Rossella Paolini, Angela Santoni, Marco Cippitelli
Summary: In this study, it was found that inhibition of neddylation using MLN4924/Pevonedistat can increase the expression of NK cell-activating ligands on the plasma membrane of MM cells, leading to enhanced NK cell degranulation. This suggests that modulation of neddylation can sensitize MM to NK cell killing, providing new insights into the anticancer activity of neddylation inhibition.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Junyi Chen, Kamila Kalinowska, Benedikt Mueller, Julia Mergner, Rainer Deutzmann, Claus Schwechheimer, Ulrich Z. Hammes, Thomas Dresselhaus
Article
Multidisciplinary Sciences
P. Marhava, A. E. L. Bassukas, M. Zourelidou, M. Kolb, B. Moret, A. Fastner, W. X. Schulze, P. Cattaneo, U. Z. Hammes, C. Schwechheimer, C. S. Hardtke
Article
Biochemistry & Molecular Biology
Ourania Lantzouni, Angela Alkofer, Pascal Falter-Braun, Claus Schwechheimer
Article
Multidisciplinary Sciences
Julia Mergner, Martin Frejno, Markus List, Michael Papacek, Xia Chen, Ajeet Chaudhary, Patroklos Samaras, Sandra Richter, Hiromasa Shikata, Maxim Messerer, Daniel Lang, Stefan Altmann, Philipp Cyprys, Daniel P. Zolg, Toby Mathieson, Marcus Bantscheff, Rashmi R. Hazarika, Tobias Schmidt, Corinna Dawid, Andreas Dunkel, Thomas Hofmann, Stefanie Sprunck, Pascal Falter-Braun, Frank Johannes, Klaus F. X. Mayer, Gerd Juergens, Mathias Wilhelm, Jan Baumbach, Erwin Grill, Kay Schneitz, Claus Schwechheimer, Bernhard Kuster
Article
Biochemistry & Molecular Biology
Hao Xu, Ourania Lantzouni, Tonko Bruggink, Rene Benjamins, Frank Lanfermeijer, Katherine Denby, Claus Schwechheimer, George W. Bassel
Article
Multidisciplinary Sciences
Julia Mergner, Martin Frejno, Maxim Messerer, Daniel Lang, Patroklos Samaras, Mathias Wilhelm, Klaus F. X. Mayer, Claus Schwechheimer, Bernhard Kuster
Article
Multidisciplinary Sciences
Lindy Abas, Martina Kolb, Johannes Stadlmann, Dorina P. Janacek, Kristina Lukic, Claus Schwechheimer, Leonid A. Sazanov, Lukas Mach, Jiri Friml, Ulrich Z. Hammes
Summary: NPA is a key inhibitor of directional auxin transport in plants, acting by directly inhibiting PINs. Research also shows an effect of NPA on PIN dimerization, offering insights into structural aspects of PINs related to their transport mechanism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Plant Sciences
Antonietta Saccomanno, Martin Potocky, Premysl Pejchar, Michal Hala, Hiromasa Shikata, Claus Schwechheimer, Viktor Zarsky
Summary: The study investigated the phosphorylation regulation of exocyst isoform EXO70C2, showing that changes in phosphorylation status can affect pollen tube growth rate and cellular architecture, with different outcomes in wild type and exo70c2 mutant cells. Phosphorylation of AtEXO70C2 does not affect its cytoplasmic localization or interaction with putative secretion inhibitor ROH1 in the yeast two-hybrid system.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Cell Biology
Ulrich Z. Hammes, Angus S. Murphy, Claus Schwechheimer
Summary: From embryogenesis to fruit formation, the accumulation and depletion of auxin through cell-to-cell transport proteins play a crucial role in regulating plant development and differentiation.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Review
Plant Sciences
Alkistis E. Lanassa Bassukas, Yao Xiao, Claus Schwechheimer
Summary: This review summarizes the current understanding of the post translational regulation of auxin efflux carriers (PINs) by AGC kinases, MAP kinases, Ca2+/CALMOD-ULIN-DEPENDENT PROTEIN KINASE-RELATED KINASEs, and receptor kinases. The proposed regulation of PINs by AGC kinases after salt stress and by stress-activated MAP kinases suggests that abiotic and biotic stress factors may modulate auxin transport and plant growth.
CURRENT OPINION IN PLANT BIOLOGY
(2022)
Article
Nutrition & Dietetics
Sarah Brajkovic, Nils Rugen, Carlos Agius, Nicola Berner, Stephan Eckert, Amirhossein Sakhteman, Claus Schwechheimer, Bernhard Kuster
Summary: Plants are crucial for sustainable global food supply, but the understanding of crop proteomes is limited. The presence of secondary metabolites in crop plants has hindered proteomic analyses, requiring individually optimized protein extraction protocols. In this study, a universal protein extraction protocol combined with an automated SP3 protocol and optimized micro-LC-MS/MS conditions was developed for high-quality proteomic analysis of crop plants. The workflow was successfully applied to analyze the proteomes of mature tomato fruits, demonstrating its robustness and potential for large-scale projects mapping crop tissue proteomes.
Article
Plant Sciences
Jan Sala, Niccolo Mosesso, Erika Isono, Claus Schwechheimer
Summary: In this study, we demonstrated that the GATA factors GNC and GNL in Arabidopsis thaliana repress starch granule growth and amyloplast differentiation in endodermal cells. Our results indicate that GNC and GNL have a complex role in starch synthesis, degradation, and starch granule initiation. Furthermore, we found that the light-regulated GNC and GNL help balance phototropic and gravitropic growth responses by repressing the growth of starch granules.
Letter
Plant Sciences
Claus Schwechheimer, Shaul Yalovsky, Viktor Zarsky
Article
Biochemistry & Molecular Biology
Samuel W. H. Koh, Petra Marhava, Surbhi Rana, Alina Graf, Bernard Moret, Alkistis E. L. Bassukas, Melina Zourelidou, Martina Kolb, Ulrich Z. Hammes, Claus Schwechheimer, Christian S. Hardtke
Summary: Angiosperms have evolved phloem for long-distance metabolite transport, involving genes like BRX related to root protophloem differentiation. The functionally divergent BRX protein family plays a crucial role, with experiments showing the importance of membrane-associated tandem BRX domains in conveying biological outputs.
Letter
Plant Sciences
David G. Robinson, Chris Hawes, Stefan Hillmer, Gerd Juergens, Claus Schwechheimer, York-Dieter Stierhof, Corrado Viotti
