Article
Biochemistry & Molecular Biology
Kim Ghilarducci, Valerie C. Cabana, Camille Desroches, Kahina Chabi, Steve Bourgault, Laurent Cappadocia, Marc P. Lussier
Summary: Protein ubiquitination plays a role in various cellular functions beyond protein degradation. The study demonstrates the interaction between RNF167 and conjugating E2 enzymes, revealing submicromolar dissociation constants and providing insights into the mechanism of binding. Additionally, the research shows that GluA2 ubiquitination by UBE2N is possible only after priming by another conjugating E2 enzyme, shedding light on the ubiquitination process mediated by RNF167.
Article
Dermatology
Shen Yan, Raphael Ripamonti, Hiroshi Kawabe, Maya Ben-Yehuda Greenwald, Sabine Werner
Summary: The ubiquitin ligase NEDD4-1 plays crucial roles in various aspects of skin function, including keratinocyte proliferation, differentiation, and wound repair. Lack of NEDD4-1 in keratinocytes leads to impaired migration and proliferation, resulting in delayed re-epithelialization of wounds. This study highlights the importance of NEDD4-1 in skin homeostasis and identifies its involvement in mitogenic and motogenic signaling pathways.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hao-Yu Chuang, Li-Yun Hsu, Chih-Ming Pan, Narpati Wesa Pikatan, Vijesh Kumar Yadav, Iat-Hang Fong, Chao-Hsuan Chen, Chi-Tai Yeh, Shao-Chih Chiu
Summary: The overexpression of NEDD4-1 in GBM and TMZ-resistant cells is associated with oncogenicity, tumorigenesis, and chemoresistance. Mechanistically, NEDD4-1 mediates the degradation of PTEN and upregulation of the AKT/NRF2/HO-1 signaling pathway, leading to increased defense against reactive oxygen species and higher resistance against TMZ treatment. Targeting this regulatory axis may help eliminate TMZ-resistant glioblastoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kai Li, Yi Niu, Yichuan Yuan, Jiliang Qiu, Yunxing Shi, Chengrui Zhong, Zhiyu Qiu, Keren Li, Zhu Lin, Zhenkun Huang, Chao Zhang, Dinglan Zuo, Wei He, Yunfei Yuan, Binkui Li
Summary: Insufficient thermal ablation can promote the progression of hepatocellular carcinoma (HCC) and upregulate the E3 ligase Nedd4. Nedd4 enhances the TGF-beta signal transduction, promoting tumor growth and metastasis. High Nedd4 expression correlates with aggressive tumor phenotypes and poor prognosis in HCC patients.
Article
Microbiology
Linliang Zhang, Shixiong Zhou, Majuan Chen, Jie Yan, Yi Yang, Linjuan Wu, Dongning Jin, Lei Yin, Mingzhou Chen, Yali Qin
Summary: The study revealed that P300-mediated NEDD4 acetylation facilitates EBOV egress, enhancing NEDD4-VP40 interactions and NEDD4 E3 ligase activity, crucial for activating VP40 ubiquitination and egress. This suggests that acetylation inhibition could be a potential drug target for Ebola virus disease treatment.
Article
Biology
Tingting Wang, Philip Woodman, Sean J. Humphrey, Janni Petersen
Summary: Cells adjust the abundance of surface nutrient transporters and receptors in response to changing nutrient environments by modulating ubiquitin-dependent endocytosis. The NEDD4 family of E3 ligases plays a role in regulating this process. In this study, the researchers discovered a novel regulation of Pub1, a member of the NEDD4-family of E3 ligases in fission yeast. They found that nitrogen stress inhibits Pub1 function, leading to an increase in the abundance of the amino acid transporter Aat1 at the plasma membrane and increased sensitivity to the toxic arginine analogue canavanine. They also found that TORC2 signalling negatively regulates Pub1, with TORC2 mutants under nutrient stress having decreased Aat1 levels and resistance to canavanine. Furthermore, they found that inhibition of TORC2 signalling increases phosphorylation of Pub1, dependent on Gsk3 activity. Overall, this study demonstrates how the TORC2 nutrient-sensing signalling network regulates Pub1 to modulate the abundance of nutrient transporters.
LIFE SCIENCE ALLIANCE
(2022)
Article
Neurosciences
Molly Hodul, Bethany J. Rennich, Eric S. Luth, Caroline L. Dahlberg, Peter Juo
Summary: This study identifies an activity-dependent mechanism that regulates WDR-20 expression and shows that WDR-20 works together with USP-46 and WDR-48 to promote surface levels of the C. elegans AMPAR GLR-1.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biology
Lu Zhu, Qing Zhang, Ciro D. Cordeiro, Sudeep Banjade, Richa Sardana, Yuxin Mao, Scott D. Emr
Summary: The study reveals a novel ubiquitination modification implemented by Rsp5 adaptor proteins, which controls the recruitment and activity of Rsp5 to facilitate the turnover of membrane proteins.
Article
Medicine, Research & Experimental
Xiaoxiao Wang, Rong Wang, Kun Jiang, Maohua Zhu, Ling Guo, Chuanyue Wu
Summary: This study identifies the critical role of PINCH-1 in regulating IGF-1R expression and skin cell behavior, and reveals a PINCH-1-NEDD4-IGF-1R signaling axis that promotes skin tumorigenesis.
Article
Cell Biology
Qi Shen, Lei Liu, Xiaotong Gu, Da Xing
Summary: Research has shown that PBM can attenuate synaptic dysfunction and neuronal death induced by A beta through MKP7-dependent suppression of JNK3, which is related to neurodegeneration. PBM also reduces amyloid load, AMPA receptor endocytosis, dendrite injury, and inflammatory responses, rescuing memory deficits in APP/PS1 mice. Mechanistically, PBM activates ERK to inactivate JNK3 by phosphorylating and stabilizing MKP7, suggesting a potential therapeutic strategy for AD.
Review
Biochemistry & Molecular Biology
Shanez Haouari, Patrick Vourc'h, Mederic Jeanne, Sylviane Marouillat, Charlotte Veyrat-Durebex, Debora Lanznaster, Frederic Laumonnier, Philippe Corcia, Helene Blasco, Christian R. Andres
Summary: This article provides a review on the roles of the 9 proteins of the HECT E3 ligase NEDD4 subfamily in the development and function of neurons in the central nervous system. These proteins are involved in the regulation of neurodevelopmental and neurodegenerative diseases and contribute to a better understanding of neuronal function and dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Elisabeth H. Thijssen, Inge M. W. Verberk, Jeroen Vanbrabant, Anne Koelewijn, Hans Heijst, Philip Scheltens, Wiesje van der Flier, Hugo Vanderstichele, Erik Stoops, Charlotte E. Teunissen
Summary: Plasma biomarkers reflecting specific Abeta proteoforms can provide valuable insights into the treatment effects of Alzheimer's disease therapies. The newly developed Amyblood assays showed similar technical and clinical performance as commercial assays, but exhibited better specificity and selectivity, making them promising for monitoring treatment response in clinical trials.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Carlos O. Oueslati Morales, Attila Ignacz, Norbert Bencsik, Zsofia Sziber, Aniko Erika Ratkai, Wolfgang S. Lieb, Stephan A. Eisler, Attila Szucs, Katalin Schlett, Angelika Hausser
Summary: The PKD family promotes AMPAR endocytosis in primary hippocampal neurons, affecting synaptic plasticity. Inhibition of PKD increases AMPAR levels at synapses, slows down their endocytic trafficking, and enhances neuronal network activity. Conversely, ectopic expression of constitutive active PKD reduces synaptic AMPAR levels but increases their colocalization with early endosomes.
Article
Cell Biology
Shuwei Hu, Yingdong Zhu, Xiaojie Zhao, Rui Li, Guangze Shao, Dongxu Gong, Chencheng Hu, Hongjun Liu, Kexin Xu, Chenxi Liu, Minghuan Xu, Zhonghua Zhao, Tao Li, Zhigang Hu, Mengle Shao, Xinwei Li, Huijuan Wu, Jing Li, Yanyong Xu
Summary: This study identifies lipocalin-2 (Lcn2) as a key regulator of hepatic scavenger receptor group B type 1 (SR-BI) and high-density lipoprotein (HDL) metabolism, and its role in atherosclerosis. Lcn2 improves HDL metabolism and alleviates atherogenesis by inhibiting Nedd4-1-mediated SR-BI ubiquitination at specific sites. Hepatocyte Lcn2 may be a promising target for improving HDL metabolism and treating atherosclerotic cardiovascular diseases.
DEVELOPMENTAL CELL
(2023)
Article
Multidisciplinary Sciences
George Kefalas, Daniela Rotin
Summary: Nedd4-1(NE) is a non-canonical isoform of Nedd4-1 that is more active and has different binding partners and substrates compared to the canonical isoform. It interacts with 14-3-3 proteins and the RPB2 subunit of RNA polymerase II.
SCIENTIFIC REPORTS
(2023)