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)
Review
Plant Sciences
Capilla Mata-Perez, Inmaculada Sanchez-Vicente, Noelia Arteaga, Sara Gomez-Jimenez, Andrea Fuentes-Terron, Cylia Salima Oulebsir, Monica Calvo-Polanco, Cecilia Oliver, Oscar Lorenzo
Summary: Environmental conditions have a significant impact on plant growth and development. Understanding the mechanisms involved in plant adaptation to abiotic stresses is crucial for improving crop production. Recent studies have shown how plants respond to various stresses through signaling networks and post-translational modifications of biological molecules, such as S-nitrosylation of proteins.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Medicine, Research & Experimental
Qiong Wang, Danping Fan, Ya Xia, Qinbin Ye, Xiaoyu Xi, Guoqiang Zhang, Cheng Xiao
Summary: The review discusses the structure, functions, and importance of RIPK1 in disease pathogenesis, highlighting the impact of activation conditions and post-translational modifications on its functions.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Feng Shu, Han Xiao, Qiu-Nuo Li, Xiao-Shuai Ren, Zhi-Gang Liu, Bo-Wen Hu, Hong-Sheng Wang, Hao Wang, Guan-Min Jiang
Summary: Autophagy has multifaceted physiological effects, acting as a protective mechanism against diseases while also having detrimental effects on normal cells. The dysregulation of autophagy-related regulators and proteins can lead to imbalanced autophagy flux, and epigenetic and post-translational modifications play a role in this process. Understanding the regulatory mechanisms of autophagy and its impact on therapeutic effectiveness is important for the development of potential targets for disease treatment.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Annachiara Tesoriere, Alberto Dinarello, Francesco Argenton
Summary: STAT3 is a crucial transcription factor regulating cell growth and proliferation by controlling gene transcription; it plays significant roles in cancer progression, with different post-translational modifications having opposite effects in different cellular models; the extensive results from various studies show that post-translational modifications drastically alter STAT3 activities, necessitating further analysis to fully elucidate its multifaceted functions.
Review
Cell Biology
Kenji Saito, Huxing Cui
Summary: The importance of estrogenic signaling in various biological processes has been well-documented. Estrogen receptor alpha (ER alpha) is a major mediator of cellular estrogenic signaling. The regulation of ER alpha gene transcription, splicing, and expression is complex, involving multiple exons and post-translational modifications. These variations have tissue-specific expression and can mediate different aspects of ER alpha signaling. The understanding of these variations in normal physiology is limited, and more studies are needed.
Review
Physiology
Kelsey S. Kalous, Sarah L. Wynia-Smith, Brian C. Smith
Summary: Increased sirtuin deacylase activity is associated with longer lifespan and lower susceptibility to aging-related diseases in eukaryotes, while decreased activity is linked to higher disease risk. Oxidative post-translational modifications such as cysteine nitrosation and glutathionylation can inhibit sirtuin deacylase activity, potentially providing a mechanistic link between cellular oxidants and age-related disease development.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Eugene Varfolomeev, Domagoj Vucic
Summary: Receptor interacting protein 1 (RIP1) kinase is a critical regulator of inflammation and cell death signaling, and its post-translational modifications, such as ubiquitination, phosphorylation, and cleavage, greatly impact its function in signaling pathways.
BIOCHEMICAL JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Julia Kraxner, Charlotta Lorenz, Julia Menzel, Iwan Parfentev, Ivan Silbern, Manuela Denz, Henning Urlaub, Blanche Schwappach, Sarah Koester
Summary: The mechanical properties of biological cells are influenced by the cytoskeleton, with phosphorylation serving as a fast mechanism for mechanical modulation. Phosphorylation can soften filaments, and the binding of 14-3-3 protein to phosphorylated filaments further enhances this effect, potentially preserving the softening and altering cell mechanics in the cell.
Article
Cell Biology
Mohd Shariq, Neha Quadir, Javaid Ahmad Sheikh, Alok Kumar Singh, William R. Bishai, Nasreen Z. Ehtesham, Seyed E. Hasnain
Summary: The host utilizes ubiquitin pathway to combat intracellular pathogens, while pathogens like Mycobacterium tuberculosis exploit this pathway to dampen host innate immune response.
Review
Biochemistry & Molecular Biology
Ze Hong, Tianchi Ma, Xing Liu, Chen Wang
Summary: Cytoplasmic microbial and host aberrant DNAs trigger host immune responses through the cGAS-STING pathway. This pathway's dysregulation is associated with autoimmune diseases, sterile inflammation, and cancers. This review summarizes the regulation of cGAS and STING, cell-specific activation, and their role in sterile inflammatory diseases, while discussing future directions and clinical applications.
Review
Cell Biology
Li Chen, Anna Kashina
Summary: Post-translational modifications (PTM) involve enzyme-mediated covalent addition of functional groups to proteins during or after synthesis, greatly increasing biological complexity and playing a crucial role in biological regulation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Qiyan Yin, Min Zheng, Qianmei Luo, Dewei Jiang, Huifeng Zhang, Ceshi Chen
Summary: Y box binding protein 1 (YB-1) is a versatile protein with important roles in gene transcription, RNA splicing, DNA damage repair, cell cycle progression, and immunity. Accumulating evidence suggests that YB-1 promotes tumor progression in various types of cancers and may serve as a potential therapeutic target.
Review
Genetics & Heredity
Gonzalo Millan-Zambrano, Adam Burton, Andrew J. Bannister, Robert Schneider
Summary: This Review discusses the impact of histone post-translational modifications (PTMs) on DNA processes and emphasizes their role in genome regulation. It explores the different ways in which PTMs can influence DNA-templated processes, such as transcription, recombination, replication, DNA repair, and genomic architecture. The review also highlights important advances in understanding how histone PTMs can exert direct or indirect effects on genome function.
NATURE REVIEWS GENETICS
(2022)
Review
Cell Biology
Rohan Gupta, Mehar Sahu, Devesh Srivastava, Swati Tiwari, Rashmi K. Ambasta, Pravir Kumar
Summary: Post-translational modifications play a crucial role in the pathogenesis of neurodegenerative diseases by regulating protein homeostasis and signaling cascades, leading to enhanced neuroprotection and potentially reversing misfolded protein accumulation.
AGEING RESEARCH REVIEWS
(2021)
Meeting Abstract
Oncology
Jennifer L. Guerriero, Gregory J. Baker, Jia-Ren Lin, Yu-An Chen, Ricardo Pastorello, Tuulia Vallius, Janae Davis, Clarence Yapp, Sarah E. Church, Eric Miller, Anniina Farkkila, Shaveta Vinayak, Melinda L. Telli, Giulia Fulci, Alan D'Andrea, Geoffrey I. Shapiro, Sara M. Tolaney, Sandro Santagata, Peter K. Sorger, Elizabeth A. Mittendorf
Article
Cell Biology
G. Kenneth Gray, Carman Man-Chung Li, Jennifer M. Rosenbluth, Laura M. Selfors, Nomeda Girnius, Jia-Ren Lin, Ron C. J. Schackmann, Walter L. Goh, Kaitlin Moore, Hana K. Shapiro, Shaolin Mei, Kurt D'Andrea, Katherine L. Nathanson, Peter K. Sorger, Sandro Santagata, Aviv Regev, Judy E. Garber, Deborah A. Dillon, Joan S. Brugge
Summary: This study presents a high-resolution breast atlas by integrating various techniques, defining different types of breast cells and their associations with breast cancer risk factors. A subset of cells associated with basal-like breast cancer was identified, and molecular factors regulating cell proportions were identified.
DEVELOPMENTAL CELL
(2022)
Article
Cell Biology
Giorgio Gaglia, Sheheryar Kabraji, Danae Rammosl, Yang Dai, Ana Verma, Shu Wang, Caitlin E. Mills, Mirra Chung, Johann S. Bergholz, Shannon Coyl, Jia-Ren Lin, Rinath Jeselsohn, Otto Metzger, Eric P. Winer, Deborah A. Dillon, Jean J. Zhao, Peter K. Sorger, Sandro Santagata
Summary: This study utilizes highly multiplexed tissue imaging to quantitatively analyze cell cycle regulators in cancer cells. The results show that proliferative architecture in tumors consists of large domains and smaller niches enriched with specific immune lineages. Some tumor cells exhibit cell cycle coherence, while others show non-canonical marker combinations. Changes in coherence are associated with oncogene activity and therapeutic intervention, and correlate with aggressive tumor behavior.
NATURE CELL BIOLOGY
(2022)
Editorial Material
Biochemical Research Methods
Denis Schapiro, Clarence Yapp, Artem Sokolov, Sheila M. Reynolds, Yu-An Chen, Damir Sudar, Yubin Xie, Jeremy Muhlich, Raquel Arias-Camison, Sarah Arena, Adam J. Taylor, Milen Nikolov, Madison Tyler, Jia-Ren Lin, Erik A. Burlingame, Young H. Chang, Samouil L. Farhi, Vesteinn Thorsson, Nithya Venkatamohan, Julia L. Drewes, Dana Pe'er, David A. Gutman, Markus D. Herrmann, Nils Gehlenborg, Peter Bankhead, Joseph T. Roland, John M. Herndon, Michael P. Snyder, Michael Angelo, Garry Nolan, Jason R. Swedlow, Nikolaus Schultz, Daniel T. Merrick, Sarah A. Mazzili, Ethan Cerami, Scott J. Rodig, Sandro Santagata, Peter K. Sorger
Summary: The imminent release of tissue atlases combining multichannel microscopy with single-cell sequencing and other omics data from normal and diseased specimens calls for data and metadata standards to guide data deposition, curation and release. The Minimum Information about Highly Multiplexed Tissue Imaging (MITI) standard, derived from best practices in genomics and microscopy, is introduced for highly multiplexed tissue images and traditional histology.
Article
Oncology
Ajit J. Nirmal, Zoltan Maliga, Tuulia Vallius, Brian Quattrochi, Alyce A. Chen, Connor A. Jacobson, Roxanne J. Pelletier, Clarence Yapp, Raquel Arias-Camison, Yu-An Chen, Christine G. Lian, George F. Murphy, Sandro Santagata, Peter K. Sorger
Summary: This study investigates immune evasion and immunoediting in primary melanoma using high-plex imaging, 3D high-resolution microscopy, and spatially resolved microregion transcriptomics. The results show significant changes in cellular neighborhoods involving tumor, immune, and stromal cells during the progression of precursor states, melanoma in situ, and invasive tumor. Immunossuppression is already detectable in precursor regions, and a suppressive environment is formed along the tumor-stromal boundary during invasion, involving cytokine gradients, MHC-II expression, and PD1-PDL1-mediated cell contacts.
Article
Biochemistry & Molecular Biology
Jia-Ren Lin, Shu Wang, Shannon Coy, Yu -An Chen, Clarence Yapp, Madison Tyler, Maulik K. Nariya, Cody N. Heiser, Ken S. Lau, Sandro Santagata, Peter K. Sorger
Summary: We used advanced imaging techniques, 3D reconstruction, spatial statistics, and machine learning to identify cell types and states associated with diagnostic and prognostic features in colorectal cancer. We found that at the tumor invasive margin, T cell suppression involves multiple cell types and that seemingly localized features such as tertiary lymphoid structures are interconnected and have graded molecular properties. These findings challenge the notion that discrete changes in tumor state are most important, demonstrating the presence of large-scale morphological and molecular gradients.
Article
Biochemistry & Molecular Biology
Fabian Froehlich, Luca Gerosa, Jeremy Muhlich, Peter K. Sorger
Summary: In this article, the mechanisms of adaptive rewiring in BRAF(V600E) melanoma cells were studied using an energy-based implementation of ordinary differential equation (ODE) modeling in combination with proteomic, transcriptomic and imaging data. Two parallel MAPK reaction channels were identified, which showed differential sensitivity to RAF and MEK inhibitors due to differences in protein oligomerization and drug binding. The study also revealed the time scale separation between immediate-early signaling and transcriptional feedback, creating a state in which the RAS-regulated MAPK channel can be activated by growth factors under conditions of fully inhibited BRAF(V600E)-driven channel. Further development of the approaches in this article is expected to yield a unified model of adaptive drug resistance in melanoma.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Caitlin E. Mills, Kartik Subramanian, Marc Hafner, Mario Niepel, Luca Gerosa, Mirra Chung, Chiara Victor, Benjamin Gaudio, Clarence Yapp, Ajit J. Nirmal, Nicholas Clark, Peter K. Sorger
Summary: The authors report a dye drop method using sequential density displacement and microscopy for multi-step assays on living cells. They used this method to collect single-cell dose-response data for small molecules in breast cancer cells. The dye drop method is rapid, reproducible, customizable, and enables the collection of information-rich perturbagen-response datasets.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Clarence Yapp, Edward Novikov, Won-Dong Jang, Tuulia Vallius, Yu-An Chen, Marcelo Cicconet, Zoltan Maliga, Connor A. Jacobson, Donglai Wei, Sandro Santagata, Hanspeter Pfister, Peter K. Sorger
Summary: This paper reports two findings that substantially improve image segmentation of tissues using a range of machine learning architectures. The inclusion of intentionally defocused and saturated images in training data and imaging the nuclear envelope using an antibody cocktail both significantly improve segmentation. These approaches have a positive impact on a wide range of tissue types and may have applications in image processing outside of microscopy.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
John A. Bachman, Benjamin M. Gyori, Peter K. Sorger
Summary: This study presents an approach to accurately assemble molecular mechanisms by using multiple natural language processing systems and INDRA, which improves the reliability of machine reading and assembles non-redundant mechanistic knowledge. Through this approach, the study extends protein-protein interaction databases and provides explanations for co-dependencies in the Cancer Dependency Map.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Chemistry, Medicinal
Changchang Liu, Peter Kutchukian, Nhan D. Nguyen, Mohammed AlQuraishi, Peter K. Sorger
Summary: This study presents a computational approach for qualitative and quantitative kinome-wide binding measurements using structure-based machine learning. The approach outperforms methods trained on crystal structures alone and structure-free methods in predicting kinase-compound interaction affinities. It also successfully captures known kinase biochemistry and generalizes well to distant kinase sequences and compound scaffolds.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Meeting Abstract
Oncology
Meri Rogava, Johannes C. Melms, Stephanie Davis, Clemens Hug, Bryan Ngo, Michael J. Lee, Patricia Ho, Amit Dipak Amin, Yiping Wang, Sean Chen, William Ge, David Liu, Thomas Tuting, Martin Rocken, Thomas K. Eigentler, Samuel F. Bakhoum, Andrei Molotkov, Akiva Mintz, Lewis C. Cantley, Peter K. Sorger, Benjamin Izar
Meeting Abstract
Oncology
Adam J. Taylor, Milen Nikolov, Ino de Brujin, Jeremy Muhlich, Mialy De Felice, Artem Sokolov, Denis Schapiro, Peter Sorger, Julie Bletz, Nikolaus Schultz, Vesteinn Thorsson, James Eddy, Ethan Cerami
Meeting Abstract
Oncology
Jia-Ren Lin, Yu-An Chen, Daniel Campton, Jeremy Cooper, Shannon Coy, Clarence Yapp, Erin McCarty, Keith L. Ligon, Steven Reese, Tad George, Sandro Santagata, Peter Sorger
Review
Oncology
Amy E. Pomeroy, Emmett V. Schmidt, Peter K. Sorger, Adam C. Palmer
Summary: Combination chemotherapy can cure certain leukemias and lymphomas, but most solid cancers are only curable at early stages. Understanding the mechanistic principles underlying curative treatments is valuable for improving future combination therapies.
