Article
Biochemistry & Molecular Biology
Ronald C. Wek, Tracy G. Anthony, Kirk A. Staschke
Summary: Organisms adapt to changing environments by engaging cellular stress response pathways, such as the integrated stress response (ISR). This review focuses on the mechanisms of eIF2 alpha kinases as first responders of stress, the regulation of eIF2 alpha phosphorylation and other stress signals, and the differential mRNA translation triggered by the ISR. It also discusses the synergy between the ISR and mTORC1 in amino acid insufficiency, as well as the pathological conditions and therapeutic strategies related to aberrant regulation of the ISR.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Cell Biology
Tamara Jimenez-Saucedo, Juan Jose Berlanga, Miguel Rodriguez-Gabriel
Summary: The imbalance of cellular proteostasis in eukaryotes affects cell lifespan, with decreased translational activity found to prolong cellular longevity, especially involving genes related to autophagy.
Review
Multidisciplinary Sciences
Ji Min Lee, Henrik M. Hammaren, Mikhail M. Savitski, Sung Hee Baek
Summary: Post-translational modifications (PTMs) on specific amino acids control the stability of target proteins. These PTM-regulated degrons act as signals for protein degradation or stabilization. This review summarizes the current knowledge of PTM-mediated protein stability regulation to enhance the identification of novel drug targets.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Simon Lizarazo, Yeeun Yook, Nien-Pei Tsai
Summary: Alzheimer's disease is a common form of dementia, characterized by the accumulation of amyloid beta peptide. This study reveals that Fmr1 is involved in A beta-induced translational suppression, leading to hyposynchrony of neuronal firing activity and loss of excitatory synapses. The mechanism involves the repression of phosphatases by Fmr1, resulting in translational suppression.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Veterinary Sciences
Ting Zhu, Xueli Jiang, Hangkuo Xin, Xiaohui Zheng, Xiaonuan Xue, Ji-Long Chen, Baomin Qi
Summary: PRV induces GADD34 expression to promote eIF2 alpha dephosphorylation, maintaining protein synthesis and facilitating viral replication.
VETERINARY RESEARCH
(2021)
Article
Microbiology
Zhaolan Ding, Teresa M. Lamb, Ahmad Boukhris, Rachel Porter, Deborah Bell-Pedersen
Summary: In the model fungus Neurospora crassa, the circadian clock regulates rhythmic protein synthesis by controlling the phosphorylation and dephosphorylation of a conserved translation initiation factor, eIF2 alpha. This temporal coordination of phosphorylation and dephosphorylation events allows for the partitioning of translation to the night, which helps coordinate energy metabolism with protein synthesis and cellular growth.
Article
Cell Biology
Albertas Navickas, Hosseinali Asgharian, Juliane Winkler, Lisa Fish, Kristle Garcia, Daniel Markett, Martin Dodel, Bruce Culbertson, Sohit Miglani, Tanvi Joshi, Keyi Yin, Phi Nguyen, Steven Zhang, Nicholas Stevers, Hun-Way Hwang, Faraz Mardakheh, Andrei Goga, Hani Goodarzi
Summary: Cancer cells exploit post-transcriptional regulatory mechanisms to achieve abnormal expression of gene networks driving metastasis. The role of translational control in cancer progression is not well understood. Using ribosome profiling, researchers compared translation efficiencies in poorly and highly metastatic breast cancer cells and patient-derived xenografts, identifying HNRNPC as a translational controller of a specific mRNA regulon. Downregulation of HNRNPC in highly metastatic cells leads to lengthening of the 3' untranslated region of HNRNPC-bound mRNAs and subsequent translational repression. Modulating HNRNPC expression affects the metastatic capacity of breast cancer cells and reduced HNRNPC expression is associated with worse prognosis in breast cancer patients.
NATURE CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Cheng Chen, Xiaobing Zhang, Yisha Wang, Xinyu Chen, Wenjie Chen, Songsong Dan, Shiqi She, Weiwei Hu, Jie Dai, Jianwen Hu, Qingyi Cao, Qianyu Liu, Yinghua Huang, Baoming Qin, Bo Kang, Ying-Jie Wang
Summary: RNA processing and translation are identified as the most differentially regulated processes between naive and primed human embryonic stem cells (hESCs) through quantitative proteomics, phosphoproteomics, and acetylproteomics analyses. Naive hESCs have a more compact proteome and can translate selective mRNAs through both eIF4E-dependent and eIF4E-independent/eIF4A2-dependent pathways. These findings contribute to a better understanding of the potential of naive hESCs and the optimization of conditions for clinical applications.
Review
Biochemistry & Molecular Biology
Yoshitaka Matsuo, Toshifumi Inada
Summary: Genetic mutations, mRNA processing errors, and lack of charged tRNAs can slow down or inhibit translating ribosomes. Monitoring systems are in place to detect and dispose of incomplete nascent chains and aberrant translation products to prevent accumulation and maintain protein homeostasis. Yeast models have been instrumental in uncovering the molecular mechanisms of these co-translational quality control systems.
Article
Multidisciplinary Sciences
Fang Zheng, Elena Lian, Gaby Ramirez, Carley McAlister, Shuo Zhou, Wen Zhang, Chunming Liu, Rushika Perera, Chang-Guo Zhan
Summary: In this study, cytotoxicity assays were performed to examine the potential cytoprotective activity of nicotine against SARS-CoV-2 infection. The results demonstrated that nicotine had no significant cytoprotective activity against SARS-CoV-2 infection in these cells.
Article
Multidisciplinary Sciences
Fang Zheng, Elena Lian, Gaby Ramirez, Carley McAlister, Shuo Zhou, Wen Zhang, Chunming Liu, Rushika Perera, Chang-Guo Zhan
Summary: This study conducted cytotoxicity assays in Vero E6 cells to examine the potential cytoprotective activity of nicotine against SARS-CoV-2 infection. The results demonstrated for the first time that nicotine had no significant cytoprotective activity against SARS-CoV-2 infection in these cells.
Article
Fisheries
Phattara-orn Havanapan, Suparat Taengchaiyaphum, Atchara Paemanee, Nuanwan Phungthanom, Sittiruk Roytrakul, Kallaya Sritunyalucksana, Chartchai Krittanai
Summary: The study showed that yellow head virus (YHV) replicates mainly in granular hemocytes in infected shrimp, with higher replication levels in GC. Comparative phosphoproteomic profiles revealed differences in the expression levels of phosphoproteins in YHV-infected GC, particularly with caspase-3 playing a crucial role in YHV replication and shrimp mortality.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Review
Oncology
Ana Gonzalez-Garcia, Antonio Garrido, Ana C. Carrera
Summary: Genetic alterations in the PI3-kinase/PTEN pathway are common in cancer cells. Current efforts to treat PTEN-dependent tumors mainly focus on PI3-kinase inhibition, but modulating PTEN post-translational modifications could provide alternative therapeutic strategies.
Article
Biochemistry & Molecular Biology
Ladislav Dokladal, Michael Stumpe, Benjamin Pillet, Zehan Hu, Guillermo Miguel Garcia Osuna, Dieter Kressler, Joern Dengjel, Claudio De Virgilio
Summary: Gcn2 protein kinase mediates cellular adaptations to amino acid limitation by phosphorylating eIF2 alpha, as well as targeting auxiliary effectors such as eIF2 G protein complex for translational control. This mechanism contributes to the inhibition of translation initiation in amino-acid-starved cells and plays a more intricate role in translation control than previously understood.
Article
Oncology
Brian P. Riesenberg, Elizabeth G. Hunt, Megan D. Tennant, Katie E. Hurst, Alex M. Andrews, Lee R. Leddy, David M. Neskey, Elizabeth G. Hill, Guillermo O. Rangel Rivera, Chrystal M. Paulos, Peng Gao, Jessica E. Thaxton
Summary: This study reveals that nutrient competition and cell stress in the tumor microenvironment can repress protein translation in T cells and impact antitumor immunity. Reprogramming T-cell metabolism can alleviate translation attenuation, improving tumor-killing capacity.
Article
Biochemistry & Molecular Biology
Robert A. Crawford, Graham D. Pavitt
Article
Cell Biology
William C. Merrick, Graham D. Pavitt
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2018)
Article
Multidisciplinary Sciences
David Talavera, Christopher J. Kershaw, Joseph L. Costello, Lydia M. Castelli, William Rowe, Paul F. G. Sims, Mark P. Ashe, Chris M. Grant, Graham D. Pavitt, Simon J. Hubbard
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Tomas Adomavicius, Margherita Guaita, Yu Zhou, Martin D. Jennings, Zakia Latif, Alan M. Roseman, Graham D. Pavitt
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Victor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G. L. Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphne Lehalle, William G. Newman, Patricia Newkirk, Judith Ranells, Miranda Splitt, Laura A. Cross, Carol J. Saunders, Bonnie R. Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka
Summary: The study uncovers the role of eIF5A in human development and disease, demonstrates the mechanistic complexity of EIF5A-related disorder, and raises possibilities for its treatment. Yeast and zebrafish experiments show that EIF5A variants cause a Mendelian disorder through reduced eIF5A-ribosome interactions, which can be partially corrected by spermidine supplementation.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Ebelechukwu C. Nwokoye, Eiman AlNaseem, Robert A. Crawford, Lydia M. Castelli, Martin D. Jennings, Christopher J. Kershaw, Graham D. Pavitt
Summary: By interacting with eIF4E and ribosomes, Caf20 influences mRNA selection and protein synthesis, with the exact mechanism remaining unclear.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Christopher J. Kershaw, Michael G. Nelson, Jennifer Lui, Christian P. Bates, Martin D. Jennings, Simon J. Hubbard, Mark P. Ashe, Chris M. Grant
Summary: This study systematically determined the protein and mRNA composition of P-bodies and stress granules before and after nutrient stress, revealing the existence of high molecular weight complexes as potential seeds for mature condensates. Shared proteins and RNA components between these biological condensates were identified, highlighting a complex interaction profile during their maturation process. The interaction networks represent a tunable response to stress, showcasing previously unrecognized condensate heterogeneity.
Article
Multidisciplinary Sciences
Christopher J. Kershaw, Martin D. Jennings, Francesco Cortopassi, Margherita Guaita, Hawra Al-Ghafli, Graham D. Pavitt
Summary: The research revealed that eIF2B can directly bind to GTP, enhancing its GEF activity towards eIF2-GDP. The K66R mutation in eIF2B gamma is particularly sensitive to guanine or GTP, indicating its potential role as a sensor of purine nucleotide availability.
Article
Biology
Robert A. Crawford, Mark P. Ashe, Simon J. Hubbard, Graham D. Pavitt
Summary: Translation regulation is an important cellular response to changing external conditions. This study identified RNA-binding proteins (RBPs) involved in translational control using polysome profiling and mass spectrometry. The results revealed previously under-appreciated RBPs and their roles in response to oxidative stress and amino acid starvation.
Article
Biochemistry & Molecular Biology
Martin D. Jennings, Priya Srivastava, Christopher J. Kershaw, David Talavera, Christopher M. Grant, Graham D. Pavitt
Summary: Cells respond to oxidative stress by reprogramming gene expression to enhance levels of antioxidant enzymes. In Saccharomyces cerevisiae, proteins Slf1 and Sro9 play a role in protein synthesis adaptation during stress. Slf1 is identified as a ribosome-associated translational modulator that promotes translation of highly-translated mRNAs, facilitating cell survival and adaptation to stress.
NUCLEIC ACIDS RESEARCH
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Victor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G. L. Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphne Lehalle, William G. Newman, Patricia Newkirk, Miranda Splitt, Judith Ranells, Laura A. Cross, Carol J. Saunders, Bonnie R. Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)