Article
Developmental Biology
Yixin Zang, Greg J. Bashaw
Summary: An affinity purification mass spectrometry was performed to establish a neural-specific Fra interactome, identifying 85 candidate proteins, most of which are conserved in humans. Many of these proteins are expressed in the ventral nerve cord, and multiple previously unreported pathways, including Lar, COP9 signalosome subunits, and Rho-5, were confirmed through gene ontology, pathway analysis, and biochemical validation. Genetic analysis demonstrates that these genes regulate axon guidance and may define unknown signaling mechanisms for Fra and Dcc.
Article
Chemistry, Multidisciplinary
Jinmin Miao, Jiajun Dong, Yiming Miao, Yunpeng Bai, Zihan Qu, Brenson A. Jassim, Bo Huang, Quyen Nguyen, Yuan Ma, Allison A. Murray, Jinyue Li, Philip S. Low, Zhong-Yin Zhang
Summary: In this study, researchers discovered the first highly potent and selective TC-PTP degrader called TP1L, which can induce degradation of TC-PTP and enhance T-cell signaling and tumor killing efficacy.
Article
Biochemistry & Molecular Biology
Kari Salokas, Xiaonan Liu, Tiina Ohman, Iftekhar Chowdhury, Lisa Gawriyski, Salla Keskitalo, Markku Varjosalo
Summary: Cell-to-cell communication is facilitated by cell surface receptor tyrosine kinases (RTKs), which phosphorylate downstream substrates in response to stimuli. Through three methods, we have mapped the molecular context and substrate profiles of RTKs, identifying new insights into their functions and interactions.
Review
Biochemistry & Molecular Biology
Vignesh Sivaganesh, Varsha Sivaganesh, Christina Scanlon, Alexander Iskander, Salma Maher, Thu Le, Bela Peethambaran
Summary: Protein tyrosine phosphatases (PTPs) have emerged as a new target in cancer therapy, with both tumor-suppressive and oncogenic properties. This review focuses on key PTPs investigated in various cancers and explores the different mechanisms underlying pro-cancerous and anti-cancerous effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Farzaneh Aboualizadeh, Zhong Yao, Jikui Guan, Luka Drecun, Shivanthy Pathmanathan, Jamie Snider, Ganesh Umapathy, Max Kotlyar, Igor Jurisica, Ruth Palmer, Igor Stagljar
Summary: This study systematically characterized the phospho-dependent ALK interactome using the MaMTH system, identifying 30 novel ALK interactors from a library of 86 SH2 domain-containing full length proteins. The interactions of these novel proteins are correlated to ALK phosphorylation activity and NCK2 was further validated as a key interactor in neuroblastoma cells. The study provides a valuable resource list of potential novel ALK signaling components for further exploration.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Cell Biology
Francisca Cornejo, Bastian I. Cortes, Greg M. Findlay, Gonzalo I. Cancino
Summary: Protein phosphatases are key regulators of signal transduction, with the LAR-RPTP subfamily playing an important role in neurobiology, from neurodevelopment to brain disorders. The LAR-RPTP subfamily consists of three members in vertebrates and is involved in various brain functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
James Adams, Benjamin P. Thornton, Lydia Tabernero
Summary: The study identified unique ligand cluster distributions specific to kinase interaction motif protein tyrosine phosphatases (KIM-PTPs) and found that ligand clusters coincide with functional and substrate binding sites in these PTPs. Ligand efficiency index (LEI) analysis showed that binders in these clusters reside in a more drug-like chemical-biological space. Differences in clusters across all KIM-PTPs highlight a distinct and specific profile for each phosphatase, with potential for exploiting unexplored allosteric functional sites for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Psychiatry
George R. Uhl
Summary: Substance use disorders pose challenges for developing effective medications due to the complex brain and pharmacological mechanisms involved, as well as genetic and environmental factors. Medical use of stimulants and opioids requires finding a balance between minimizing their contribution to substance use disorders while retaining their benefits for various medical conditions. The data needed for assessing abuse liability and regulatory scheduling differs from that needed for licensing anti-addiction medications, adding further complexity. This article discusses the challenges in developing pentilludin as a novel anti-addiction therapeutic, targeting the protein tyrosine phosphatase D (PTPRD), which is supported by genetic and pharmacologic studies in humans and mice.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Cell Biology
Zhe Qian, Dongyan Song, Jonathan J. Ipsaro, Carmelita Bautista, Leemor Joshua-Tor, Johannes T. -H. Yeh, Nicholas K. Tonks
Summary: In this study, the researchers generated a novel monoclonal antibody, RD-43, which targeted the ectodomain of PTPRD to inhibit its function and promote its degradation. Treatment with RD-43 was found to suppress SRC signaling required for breast cancer cell invasion. These findings suggest that antibodies targeting extracellular segments of receptor protein tyrosine phosphatases may have therapeutic potential.
GENES & DEVELOPMENT
(2023)
Review
Cell Biology
Michel L. Tremblay
Summary: In this study, a monoclonal antibody targeting PTPRD was identified, which induced dimerization and inhibition of the phosphatase activities of PTPRD and led to its proteolysis by intracellular degradation pathways. This finding opens up a new framework for the clinical manipulation of PTPRD and its closely related family members.
GENES & DEVELOPMENT
(2023)
Article
Oncology
Xinyan Wu, Li Wang, Nicole A. Pearson, Santosh Renuse, Ran Cheng, Ye Liang, Dong-Gi Mun, Anil K. Madugundu, Yaoyu Xu, Parkash S. Gill, Akhilesh Pandey
Summary: This study utilized mass spectrometry-based proteomics to quantify cancer signaling regulated by AXL activation, identifying over 1000 phosphotyrosine sites and upregulation of cancer-promoting and cell migration pathways. Rapid phosphorylation of multiple receptor tyrosine kinases and protein tyrosine phosphatases was observed upon GAS6 stimulation. The study provides insights into AXL's oncogenic role and potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Lisa M. Petti, Benjamin N. Koleske, Daniel DiMaio
Summary: Most eukaryotic transmembrane and secreted proteins contain N-terminal signal peptides that facilitate membrane insertion and subsequent degradation. A small hydrophobic protein can act as a signal peptide while retaining transforming activity, interacting with target protein transmembrane domains. This finding suggests that naturally occurring signal peptides may have additional biological activities.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Yi Xin (Iris) Tu, Andrew M. Sydor, Etienne Coyaud, Estelle M. N. Laurent, Diana Dyer, Nora Mellouk, Jonathan St-Germain, Robert M. Vernon, Julie D. Forman-Kay, Taoyingnan Li, Rong Hua, Kexin Zhao, Neale D. Ridgway, Peter K. Kim, Brian Raught, John H. Brumell
Summary: This study identified a network of interactions among core human macroautophagy proteins using proximity-dependent biotin identification, highlighting the critical role of OSBPL family members in the macroautophagy process.
Article
Biochemistry & Molecular Biology
Sophie Rizzo, Eden Sikorski, Soohyung Park, Wonpil Im, Victor Vasquez-Montes, Alexey S. Ladokhin, Damien Thevenin
Summary: Cell signaling mediated by receptor protein tyrosine kinases (RTKs) is regulated by receptor protein tyrosine phosphatases (RPTPs). Disrupting the interaction between RPTP and RTKs can antagonize RTK-driven cell phenotypes. Researchers have designed and tested pH-responsive TM peptide agonists of a representative RPTP member, PTPRJ, which effectively reduce EGFR phosphorylation and inhibit cancer cell migration and proliferation.
Article
Biochemistry & Molecular Biology
Sophie Rizzo, Eden Sikorski, Soohyung Park, Wonpil Im, Victor Vasquez-Montes, Alexey S. Ladokhin, Damien Thevenin
Summary: Research shows that the homodimerization of the RPTP family member PTPRJ is regulated by specific transmembrane residues. pH-responsive TM peptide agonists of PTPRJ can inhibit RTK-driven cancer cell migration and proliferation, providing a potentially transformative approach to studying selectivity mechanisms.
Article
Biochemistry & Molecular Biology
Mark F. Mabanglo, Keith S. Wong, Marim M. Barghash, Elisa Leung, Stephanie H. W. Chuang, Afshan Ardalan, Emily M. Majaesic, Cassandra J. Wong, Shen Zheng, Henk Lang, Donald S. Karanewsky, Andrew A. Iwanowicz, Lee M. Graves, Edwin J. Iwanowicz, Anne-Claude Gingras, Walid A. Houry
Summary: The mitochondrial ClpP protease is involved in mitochondrial protein quality control and is required for eliminating ROS-damaged proteins in cancer cells. Targeting ClpP using small-molecule agonists is a new strategy in cancer therapy. Structural and molecular studies provide insight into how dysregulated ClpP affects cancer cell viability and proliferation.
Article
Medicine, General & Internal
Weixin Zhao, Ailing Song, Yang Xu, Qian Wu, Cuicui Liu, Jiani C. C. Yin, Qiuxiang Ou, Xue Wu, Yang Shao, Xinmin Zhao
Summary: This retrospective study analyzed next-generation sequencing (NGS) data from 1025 non-small cell lung cancer (NSCLC) patients with compound epidermal growth factor receptor (EGFR) mutations. Different subtypes of compound EGFR mutations were associated with distinct clinical features, genetic architectures, and prognostic outcomes. Rare mutation-dominant subtypes with variations of uncertain significance (VUSs) residing in the kinase domain had poor clinical outcomes and implied disruptions in kinase domain regulation/function.
Article
Multidisciplinary Sciences
Natalia Martin-Orozco, Noah Vale, Alan Mihic, Talya Amor, Lawrence Reiter, Yuko Arita, Reuben Samson, Queenie Hu, Anne-Claude Gingras, Bradley Thomas Sorenson, Eric Gates Marcusson, Piyush Patel
Summary: To address the limited access to SARS-CoV-2 vaccines in poor countries during the COVID-19 pandemic, a low-cost mRNA vaccine called PTX-COVID19-B was developed and evaluated in a Phase 1 trial. The vaccine encoded the Spike protein D614G variant without the proline-proline (986-987) mutation present in other COVID-19 vaccines. The study aimed to assess the safety, tolerability, and immunogenicity of the PTX-COVID19-B vaccine in healthy seronegative adults aged 18-64 years.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Yi-Chan J. Lin, David H. Evans, Ninette F. Robbins, Guillermo Orjuela, Kento T. Abe, Bhavisha Rathod, Karen Colwill, Anne-Claude Gingras, Ashleigh Tuite, Qi-Long Yi, Sheila F. O'Brien, Steven J. Drews
Summary: The study found that vaccinated individuals have a higher neutralizing capacity against Omicron BA.1 compared to unvaccinated individuals. Neutralization assays showed that plasma with a higher level of anti-SARS-CoV-2 antibodies provides protection against Omicron BA.1 infection.
MICROBIOLOGY SPECTRUM
(2023)
Article
Medicine, General & Internal
Lucie Richard, Rosane Nisenbaum, Michael Brown, Michael Liu, Cheryl Pedersen, Jesse I. R. Jenkinson, Sharmistha Mishra, Stefan Baral, Karen Colwill, Anne-Claude Gingras, Allison McGeer, Stephen W. Hwang
Summary: This study aimed to quantify the incident infection rate of SARS-CoV-2 among people experiencing homelessness in Toronto in 2021 and 2022, and to assess factors associated with infection. The study found that the infection rate of SARS-CoV-2 was high among homeless individuals, especially after the emergence of the Omicron variant. The study suggests the need for increased focus on homelessness prevention to better protect these communities.
Editorial Material
Biochemistry & Molecular Biology
Weidong Wang, Wang Lv, Hui Wang, Yang Xu, Junrong Yan, Han-Ming Shen, Liqun Shan, Jian Hu
Article
Medicine, General & Internal
Tanya J. Murphy, Hanna Swail, Jaspreet Jain, Maureen Anderson, Philip Awadalla, Lesley Behl, Patrick E. Brown, Carmen L. Charlton, Karen Colwill, Steven J. Drews, Anne-Claude Gingras, Deena Hinshaw, Prabhat Jha, Jamil N. Kanji, Victoria A. Kirsh, Amanda L. S. Lang, Marc-Andre Langlois, Stephen Lee, Antoine Lewin, Sheila F. O'Brien, Chantale Pambrun, Kimberly Skead, David A. Stephens, Derek R. Stein, Graham Tipples, Paul G. Van Caeseele, Timothy G. Evans, Olivia Oxlade, Bruce D. Mazer, David L. Buckeridge
Summary: During the first year of the COVID-19 pandemic, less than 6% of reported cases in Canada were COVID-19. Despite high vaccine coverage achieved by fall 2021, the Omicron variant caused a surge in infections, overwhelming testing capacity and making it difficult to determine population immunity trajectory.
CANADIAN MEDICAL ASSOCIATION JOURNAL
(2023)
Article
Hematology
Danya Shen, Biqi Zhou, Meng Shan, Xuekai Li, Mengqian Chu, Yifan Shen, Yuchen Zhan, Jie Xu, Depei Wu, Yang Xu
Summary: Chimeric antigen receptor-modified T cell (CAR-T) therapy is a promising immunotherapy for hematologic malignancies, but diagnosing infection after CAR-T infusion (CTI) is challenging. Plasma metagenomic next-generation sequencing (mNGS) has been shown to be a reliable diagnostic approach for infection. In this study, the diagnostic performance of mNGS for infection in the first 30 days after CTI was investigated, and it was found that mNGS had a sensitivity of 69.2% and specificity of 89.2%.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Correction
Biochemistry & Molecular Biology
Elise Vickridge, Camila C. F. Faraco, Payman S. Tehrani, Zubaidah M. Ramdzan, Billel Djerir, Hedyeh Rahimian, Lam Leduy, Alexandre Marechal, Anne-Claude Gingras, Alain Nepveu
Article
Biochemical Research Methods
Kevin W. Cormier, Brett Larsen, Anne-Claude Gingras, James R. Woodgett
Summary: This study investigates the functional differentiation of two isoforms of GSK-3 and identifies novel interaction partners using affinity purification and proximity-dependent biotinylation mass spectrometry methods. The interactomes of the two isoforms are highly similar in HEK293 cells, but there are isoform-specific interactions in HeLa cells. Understanding the differences in interactions between the isoforms may provide insights into their distinct functions and regulation, and open up possibilities for isoform-specific strategies.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Respiratory System
Yu Yao, Huaping Yang, Bo Zhu, Song Wang, Jiaohui Pang, Xiaoying Wu, Yang Xu, Junli Zhang, Jinfeng Zhang, Qiuxiang Ou, Hui Tian, Zheng Zhao
Summary: This study found that MET tyrosine kinase domain (TKD) mutations were detected in both baseline and patients treated with TKIs in non-small-cell lung cancer (NSCLC) patients. MET-H1094Y may be associated with acquired resistance after recurrent EGFR-TKIs treatment. Preliminary data suggests that EGFR-mutated NSCLC patients who acquired MET-V1092I or MET-H1094Y may benefit from combinatorial therapy with EGFR-TKI and MET-TKI, providing new insights into personalized medical treatment.
RESPIRATORY RESEARCH
(2023)
Article
Medicine, Research & Experimental
Yihan Ding, Chang Liu, Yiming Cai, Chang Hou, Guanghua Chen, Yang Xu, Shaoyan Hu, Depei Wu
Summary: Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have shown to be an effective treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD) with a high response rate and good survival rate.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Amanda Ng, Fabian Offensperger, Jose A. Cisneros, Natalie S. Scholes, Monika Malik, Ludovica Villanti, Andrea Rukavina, Evandro Ferrada, J. Thomas Hannich, Anna Koren, Stefan Kubicek, Giulio Superti-Furga, Georg E. Winter
Summary: This study develops a high-throughput workflow for the discovery of molecular glue degraders (MGDs) that target nonessential proteins. By synthesizing a compound library and using a morphological profiling assay, the researchers identified a CRBN-dependent MGD FL2-14 that targets the nonessential protein GSPT2. The workflow is expected to contribute to the discovery and characterization of MGDs that target a wider range of proteins.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Analytical
Ci Wu, Jiao Lei, Fei Meng, Xingyao Wang, Cassandra J. Wong, Jiaxi Peng, Ge Lin, Anne-Claude Gingras, Junfeng Ma, Shen Zhang
Summary: This study explores the applicability of turboDDA for quantitative proteomics of trace samples and finds that turboDDA exhibits better sensitivity. The accuracy and reproducibility of iTRAQ-labeled trace samples are evaluated, showing improved quantification accuracy and reproducibility with turboDDA.
ANALYTICAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Wei Wei, Fangfang Shi, Yang Xu, Yang Jiao, Ying Zhang, Qiuxiang Ou, Xue Wu, Lingyi Yang, Jinhuo Lai
Summary: Next-generation sequencing was used to investigate molecular features in NSCLC patients with pathogenic/likely pathogenic ATM/ATR mutations. The results were validated using an external cohort of NSCLC patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)