Article
Neurosciences
Maria J. Pinto, Diogo Tome, Ramiro D. Almeida
Summary: Ubiquitin tagging plays a crucial role in determining the fate of proteins, especially in neurons where it is exploited for various cellular demands. The ubiquitin signaling pathway is fundamental in neurodevelopment and mature brain function, yet the specific role of ubiquitin in axonal biology remains less explored.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Xiang Chen, Zaw Min Htet, Erika Lopez-Alfonzo, Andreas Martin, Kylie J. Walters
Summary: The 26S proteasome is responsible for regulated proteolysis in eukaryotic cells, with substrates targeted to it through post-translational modification with ubiquitin. Deubiquitinating enzymes (DUBs) play a crucial role in catalyzing ubiquitin chain hydrolysis, coupling deubiquitination to substrate unfolding and degradation. This intricate machinery of proteasomes and ubiquitin-modified substrates remains an active area of investigation, with potential for therapeutic targeting.
Article
Biochemistry & Molecular Biology
Chia-Cheng Kan, Azucena Mendoza-Herrera, Julien Levy, J. Joe Hull, Jeffery A. Fabrick, Cecilia Tamborindeguy
Summary: This study identified HPE1 as a suppressor of plant immunity and showed its interaction with tomato RAD23 proteins, suggesting a role in virulence in Lso pathogenesis by perturbing the ubiquitin-proteasome system. The study also observed earlier colonization and symptom development in HPE1 overexpressing plants infected with Lso haplotype B.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chenliang Zhang, YiChun Duan, Chen Huang, Liping Li
Summary: This study explores the role of SQSTM1 phosphorylation in the formation of aggresomes under proteasome inhibition. It finds that inhibiting SQSTM1 S403 phosphorylation promotes the formation of aggresomes for ubiquitinated proteins, while phosphorylation of SQSTM1 T269/S272 inhibits S403 phosphorylation and enhances aggresome formation, protecting cells from proteotoxicity.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2023)
Article
Cell Biology
Xiaoli Wu, Yanrong Zheng, Mengru Liu, Yue Li, Shijia Ma, Weidong Tang, Wenping Yan, Ming Cao, Wanqing Zheng, Lei Jiang, Jiaying Wu, Feng Han, Zhenghong Qin, Liang Fang, Weiwei Hu, Zhong Chen, Xiangnan Zhang
Summary: Mitophagy is essential for promoting neuronal survival in cerebral ischemia, and the deficiency of mitophagy receptor BNIP3L/NIX can lead to increased brain injury in ischemic conditions. The degradation of BNIP3L by proteasomes in ischemic brains contributes to mitophagy deficiency, and pharmacological intervention targeting this process, such as using the proteasome inhibitor carfilzomib, can rescue mitophagy and protect against ischemic brain injury.
Article
Cell Biology
Jana Petrusova, Robert Havalda, Petr Flachs, Tomas Venit, Alzbeta Darasova, Lenka Hulkova, Martin Sztacho, Pavel Hozak
Summary: In this study, the presence of Vinculin (VCL) in the nucleus of spermatocytes and its involvement in proper meiotic division were demonstrated. The study also suggests the potential role of VCL in spermatogenesis through regulation of the ubiquitin-proteasome pathway.
Article
Multidisciplinary Sciences
Tiina Ohman, Lisa Gawriyski, Sini Miettinen, Markku Varjosalo, Sirpa Loukovaara
Summary: System pathology analysis of vitreous proteins in patients with rhegmatogenous retinal detachment revealed specific proteome profiles compared to other eye diseases, indicating activation of mechanisms like glycolysis, photoreceptor death, and signaling pathways to promote retinal cell survival. Additionally, platelet-mediated wound healing processes, reorganization of cell adhesion molecules, and apoptotic processes were also detected during disease progression.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Katarina Ziakova, Maria Kovalska, Ivana Pilchova, Katarina Dibdiakova, Maria Brodnanova, Michal Pokusa, Dagmar Kalenska, Peter Racay
Summary: A transient global brain ischemia leads to selective ischemic neurodegeneration, and the mechanism of such selective and delayed neurodegeneration is still uncertain. This study focused on the involvement of proteasomal and endoplasmic reticulum (ER) stress in ischemic neurodegeneration. Laser scanning confocal microscopy analysis was performed on brain slices from animals underwent global brain ischemia. The results suggest dysfunction of the ubiquitin proteasome system and consequent p53-induced expression of PUMA as the main mechanisms responsible for selective and delayed degeneration of hippocampal pyramidal neurons.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stefan Milde, Guy C. Brown
Summary: This study suggests that microglial phagocytosis of stressed neurons mediated by P2Y(6) receptor plays a role in the delayed neuronal loss after stroke, and targeting the P2Y(6) receptor could potentially prevent peri-infarct neuronal loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sinem Demirbag-Sarikaya, Yunus Akkoc, Sila Turgut, Secil Erbil-Bilir, Nur Mehpare Kocaturk, Joern Dengjel, Devrim Gozuacik
Summary: The maintenance of cellular homeostasis requires a balance between anabolic and catabolic reactions. Autophagy, a major catabolic reaction, is activated by various stressors, including DNA damage. This study demonstrates a novel interaction between the autophagy protein ATG5 and the DNA repair protein Ku70, which is crucial for DNA repair and recovery from genotoxic stress.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Jing Cheng, Huancheng Zheng, Chenyu Liu, Jiabin Jin, Zhenkai Xing, Yili Wu
Summary: Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia in the elderly. The Ubiquitin proteasome system (UPS) is critical in AD pathogenesis, and UBE2O, a major component of UPS, shows reduced expression with age and in AD mice. Increasing UBE2O expression or activity may be a potential approach for AD treatment by inhibiting neuronal death.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Cell Biology
Mohamed A. Eldeeb, Wenbin Zhou, Mansoore Esmaili, Alaa M. Elgohary, Hai Wei, Richard P. Fahlman
Summary: Cellular signalling leads to apoptotic pathways and caspase activation, resulting in the generation of protein fragments with new functions. These proteolytically activated protein fragments can be degraded by the N-degron degradation pathways. The stability of the pro-apoptotic fragment of PKC-theta was investigated, revealing that it is unstable due to its N-terminal lysine targeting it for proteasomal degradation. Inhibition of N-degron degradation enhanced the apoptosis-inducing effect of staurosporine.
CELLULAR SIGNALLING
(2023)
Article
Multidisciplinary Sciences
Rommel J. Gestuveo, Jamie Royle, Claire L. Donald, Douglas J. Lamont, Edward C. Hutchinson, Andres Merits, Alain Kohl, Margus Varjak
Summary: The authors developed mosquito cell lines expressing Zika virus (ZIKV) capsid and conducted proteomics experiments, identifying 157 protein interactors, with 8 shown to act as pro-viral factors, demonstrating the transitional endoplasmic reticulum 94 (TER94) and its human ortholog VCP target ZIKV capsid to proteasomal degradation to facilitate infection.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Hye Ji Jang, Kwang Chul Chung
Summary: This study reveals a dynamic interplay between ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP) in neurotoxin-based cell death models of Parkinson's disease, indicating their involvement in regulating cell death pathways.
Article
Cell Biology
Shubhangini Tiwari, Abhishek Singh, Parul Gupta, Sarika Singh
Summary: This study reveals the crucial role of UBA52 in regulating protein aggregation and cell death in Parkinson's disease pathology. UBA52 interacts with alpha-synuclein, HSP90, and E3-ubiquitin ligase CHIP, and co-localizes with alpha-synuclein in the mitochondrion. Furthermore, UBA52 plays an essential role in HSP90 ubiquitylation.
Article
Biochemistry & Molecular Biology
Hao Liu, Jie Chen, Wenjin Li, Marie E. Rose, Sunita N. Shinde, Manimalha Balasubramani, Guy T. Uechi, Buelent Mutus, Steven H. Graham, Robert W. Hickey
Article
Cell Biology
H. Liu, W. Li, M. E. Rose, R. W. Hickey, J. Chen, G. T. Uechi, M. Balasubramani, B. W. Day, K. V. Patel, S. H. Graham
CELL DEATH & DISEASE
(2015)
Article
Biochemistry & Molecular Biology
Hao Liu, Marie E. Rose, Sherman Culver, Xiecheng Ma, C. Edward Dixon, Steven H. Graham
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2016)
Article
Cell Biology
Steven H. Graham
NEURAL REGENERATION RESEARCH
(2016)
Article
Multidisciplinary Sciences
Hao Liu, Marie E. Rose, Xiecheng Ma, Sherman Culver, C. Edward Dixon, Steven H. Graham
Review
Neurosciences
Milos D. Ikonomovic, Eric E. Abrahamson, Shaun W. Carlson, Steven H. Graham, C. Edward Dixon
Article
Biochemical Research Methods
Jafar Sadik B. Shaik, Tricia M. Miller, Steven H. Graham, Mioara D. Manole, Samuel M. Poloyac
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2014)
Article
Critical Care Medicine
Patrick M. Kochanek, Travis C. Jackson, Ruchira M. Jha, Robert S. B. Clark, David O. Okonkwo, Hulya Bayir, Samuel M. Poloyac, Amy K. Wagner, Philip E. Empey, Yvette P. Conley, Michael J. Bell, Anthony E. Kline, Corina O. Bondi, Dennis W. Simon, Shaun W. Carlson, Ava M. Puccio, Christopher M. Horvat, Alicia K. Au, Jonathan Elmer, Amery Treble-Barna, Milos D. Ikonomovic, Lori A. Shutter, D. Lansing Taylor, Andrew M. Stern, Steven H. Graham, Valerian E. Kagan, Edwin K. Jackson, Stephen R. Wisniewski, C. Edward Dixon
JOURNAL OF NEUROTRAUMA
(2020)
Article
Multidisciplinary Sciences
Hao Liu, Nadya Povysheva, Marie E. Rose, Zhiping Mi, Joseph S. Banton, Wenjin Li, Fenghua Chen, Daniel P. Reay, German Barrionuevo, Feng Zhang, Steven H. Graham
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Clinical Neurology
Fenghua Chen, Zhongfang Weng, Qinghai Xia, Catherine Cao, Rehana K. Leak, Lihong Han, Jian Xiao, Steven H. Graham, Guodong Cao
TRANSLATIONAL STROKE RESEARCH
(2019)
Article
Neurosciences
Zhiping Mi, Hao Liu, Marie E. Rose, Xiecheng Ma, Daniel P. Reay, Jie Ma, Jeremy Henchir, C. Edward Dixon, Steven H. Graham
Summary: UCHL1 is a multifunctional protein expressed at high levels in neurons throughout the brain, with its hydrolase activity playing a crucial role in the recovery after neuronal injury and the pathogenesis of neurodegenerative diseases.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Neurosciences
Zhiping Mi, Hao Liu, Marie E. Rose, Jie Ma, Daniel P. Reay, Xiecheng Ma, Jeremy J. Henchir, C. Edward Dixon, Steven H. Graham
Summary: The study found that mutating cysteine to alanine at site 152 of UCHL1 can reduce protein ubiquitination, decrease activation of autophagy markers, improve abnormal axons and cell death, and enhance motor and cognitive function after traumatic brain injury. This research provides a new target for future therapeutic approaches in TBI.
Article
Cell Biology
Zhiping Mi, Steven H. Graham
Summary: This review focuses on the potential role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury and recovery. It discusses the normal physiological functions of UCHL1, the effects of posttranslational modification sites and splice variants on UCHL1 function, mouse models with UCHL1 mutations and deletions, and the hypothesized role and pathogenic mechanisms of UCHL1 in neurodegenerative diseases and brain injury.
AGEING RESEARCH REVIEWS
(2023)
Meeting Abstract
Endocrinology & Metabolism
Z. Mi, N. Povysheva, M. Rose, J. Ma, D. Zeh, N. Harikumar, I. Bhuiyan, S. Graham
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Review
Cell Biology
Steven H. Graham, Hao Liu
AGEING RESEARCH REVIEWS
(2017)