Article
Neurosciences
Andreas Hentschel, Nancy Meyer, Nicolai Kohlschmidt, Claudia Gross, Albert Sickmann, Ulrike Schara-Schmidt, Fabian Foerster, Ana Topf, Jon Christiansen, Rita Horvath, Matthias Vorgerd, Rachel Thompson, Kiran Polaparapu, Hanns Lochmuller, Corinna Preusse, Luis Hannappel, Anne Schaenzer, Anika Grueneboom, Andrea Gangfuss, Andreas Roos
Summary: PPP1R21 is a co-factor for PP1 and its mutation leads to a neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities. Impaired vesicular transport and activation of the ubiquitin-proteasome system were identified as the pathomechanisms. Proteomic analysis revealed dysregulation of proteins related to cellular stress burden and neurological functions in PPP1R21-mutant fibroblasts, which may contribute to the milder phenotype observed in some patients.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Siobhan S. Pattwell, Sonali Arora, Nicholas Nuechterlein, Michael Zager, Keith R. Loeb, Patrick J. Cimino, Nikolas C. Holland, Noemi Reche-Ley, Hamid Bolouri, Damian A. Almiron Bonnin, Frank Szulzewsky, Vaishnavi V. Phadnis, Tatsuya Ozawa, Michael J. Wagner, Michael C. Haffner, Junyue Cao, Jay Shendure, Eric C. Holland
Summary: This article highlights the previously unidentified role of the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis. TrkB.T1 is an important isoform in these processes and is expressed in both embryonic and adult tumors. The study also reveals its interaction with developmental and oncogenic signaling pathways, suggesting its potential to reshape our understanding of developmental systems and oncology.
Article
Medicine, Research & Experimental
Jin Zeng, Hua Xu, Chunhua Huang, Yi Sun, Haibing Xiao, Gan Yu, Hui Zhou, Yangjun Zhang, Weimin Yao, Wei Xiao, Junhui Hu, Lily Wu, Jinchun Xing, Tao Wang, Zhiqiang Chen, Zhangqun Ye, Ke Chen
Summary: This study found that exclusion of CD46 exon 13 is significantly increased in bladder cancer samples, with different splice variants of CD46 showing varied effects on tumor growth, migration, and tumorigenicity. By utilizing interaction proteomics, new CD46-interacting proteins were identified, revealing a potential role for CD46 in regulating mRNA translation through interaction with the translation machinery. Furthermore, a novel interaction between heterogeneous nuclear ribonucleoprotein (hnRNP)A1 and the CYT2 domain of CD46 was discovered, impacting the translation of HIF1a and c-Myc.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Biochemistry & Molecular Biology
Noelia Miret, Lorena Zarate, Fernando Erra Diaz, M. Agustina Leguizamon, Carolina A. Pontillo, Florencia A. Chiappini, Leandro Ceballos, Jorge Geffner, Andrea S. Randi
Summary: A reduction in extracellular pH promotes breast cancer progression by activating the AhR/c-Src axis, which increases cell migration and MMP-9 activity.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Zhaotong Cong, Fulai Zhou, Chao Zhang, Xinyu Zou, Huibing Zhang, Yuzhe Wang, Qingtong Zhou, Xiaoqing Cai, Qiaofeng Liu, Jie Li, Lijun Shao, Chunyou Mao, Xi Wang, Jihong Wu, Tian Xia, Li-Hua Zhao, Hualiang Jiang, Yan Zhang, H. Eric Xu, Xi Cheng, Dehua Yang, Ming-Wei Wang
Summary: The study found that a splice variant (SV1) of the human growth hormone-releasing hormone receptor is capable of transducing biased signal, selectively coupling to beta-arrestins while the main receptor activates Gs. Differences at the receptor N terminus lead to distinct downstream signaling pathways for GHRHR and SV1, with GHRHR predominantly activating Gs and SV1 selectively coupling to beta-arrestins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Olga Shatokhina, Valeriia Kovalskaia, Peter Sparber, Inna Sharkova, Irina Mishina, Vera Kuznetsova, Oxana Ryzhkova
Summary: This study reports a novel splice variant in the TRA2B gene identified in a patient with seizures and neurodevelopmental delay. It confirms previous conclusions and highlights the importance of this research. Comprehensive genetic testing reveals the pathogenic nature of the variant and its clinical presentation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Priscilia Lianto, Samantha A. Hutchinson, J. Bernadette Moore, Thomas A. Hughes, James L. Thorne
Summary: A study revealed seven LXR splice variants, five of which were prognostic for disease-free survival in breast cancer patients; while full-length LXR alpha splice variants were associated with poor prognosis, truncated LXR alpha splice variants or any LXR beta splice variant were linked to longer survival.
Article
Pathology
Donna C. Ferguson, Douglas A. Mata, Timothy Ky Tay, Tiffany A. Traina, Ayca Gucalp, Sarat Chandarlapaty, Timothy M. D'Alfonso, Edi Brogi, Kerry Mullaney, Marc Ladanyi, Maria E. Arcila, Ryma Benayed, Dara S. Ross
Summary: The prevalence of AR-V7 in breast cancer is 9.7%, with a correlation to AR positivity and apocrine morphology. Notably, AR-V7 was detected in both primary and metastatic/recurrent breast cancer patients without prior endocrine therapy, suggesting potential implications for targeted treatment.
Article
Oncology
Jiaqian Liang, Liyang Wang, Larysa Poluben, Mannan Nouri, Seiji Arai, Lisha Xie, Olga S. Voznesensky, Laura Cato, Xin Yuan, Joshua W. Russo, Henry W. Long, Myles Brown, Shaoyong Chen, Steven P. Balk
Summary: In castration-resistant prostate cancer (CRPC), the splice variant ARv7 can function independently of the full length ARfl, with both contributing independently to overall AR activity.
Article
Biochemistry & Molecular Biology
Esraa Haji, Saeed Al Mahri, Yumna Aloraij, Shuja Shafi Malik, Sameer Mohammad
Summary: ADR beta(3) is a crucial receptor involved in lipid metabolism regulation, with a genetic variant W64R linked to diabetes and obesity, showing no significant functional differences compared to the wild-type counterpart.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Samuel Koller, Tim Beltraminelli, Jordi Maggi, Agnes Wlodarczyk, Silke Feil, Luzy Baehr, Christina Gerth-Kahlert, Moreno Menghini, Wolfgang Berger
Summary: X-linked retinitis pigmentosa (XLRP) caused by mutations in the RPGR gene is one of the most severe forms of RP due to its early onset and intractable progression. Most cases have been associated with genetic variants within the purine-rich exon ORF15 region of this gene. RPGR retinal gene therapy is currently being investigated in several clinical trials. Therefore, it is crucial to report and functionally characterize (all novel) potentially pathogenic DNA sequence variants. Whole-exome sequencing (WES) was performed for the index patient. The splicing effects of a non-canonical splice variant were tested on cDNA from whole blood and a minigene assay. Transcript analyses with minigene assays and cDNA from peripheral blood are useful tools for the characterization of splicing defects due to variants in the RPGR and may increase the diagnostic yield in RP. The functional analysis of non-canonical splice variants is required to classify those variants as pathogenic according to the ACMG's criteria.
Article
Plant Sciences
Yuhong Li, Shuying Hu, Yueqi Chen, Xing Zhang, Hanchi Gao, Jing Tian, Jian Chen
Summary: A novel estrogen receptor-alpha splice variant ER-α30 was found to be primarily localized in the nucleus of triple-negative breast cancer (TNBC) cells. ER-α30 was significantly overexpressed in breast cancer tissues of ER- and progesterone receptor (PR)-negative subtype as well as in TNBC cell lines compared to normal breast cell line MCF10A. ER-α30 overexpression promoted TNBC cell viability, migration, invasion, and epithelial-mesenchymal transition, while knockdown of ER-α30 had the opposite effects. Calycosin could suppress ER-α30 expression and inhibit TNBC growth and metastasis.
Article
Biology
Yi-Chun Kao, Yi-Wen Chang, Charles P. Lai, Nai-Wen Chang, Chen-Hao Huang, Chien-Sheng Chen, Hsuan-Cheng Huang, Hsueh-Fen Juan
Summary: This study reveals that cancer cells express higher levels of eATP synthase under starvation stress, leading to increased production of EVs. The eATP synthase generates extracellular ATP to stimulate EV secretion by enhancing P2X(7) receptor-triggered Ca2+ influx. Surprisingly, eATP synthase is also found on the surface of tumor-secreted EVs. The eATP synthase-coated EVs increase uptake by immune cells and inhibit their proliferation and cytokine release.
COMMUNICATIONS BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Kimberley D. Katleba, Paramita M. Ghosh, Maria Mudryj
Summary: Multiple studies have shown the importance of androgen receptor (AR) splice variants (SVs) in prostate cancer progression and their diagnostic utility. However, studies have found that AR-SVs are also expressed in non-prostatic malignancies and have diverse roles in tumorigenesis. AR-SVs also play a role in non-cancer pathologies.
Article
Biochemistry & Molecular Biology
Liora Jacobs Catane, Ofra Moshel, Yoav Smith, Ben Davidson, Reuven Reich
Summary: By knocking out different TGF beta receptor splice variants, it was found that T beta RIv1 and T beta RIIv1 had different effects on the migration, invasion, and ROS production of ovarian carcinoma cells. There were significant changes in protein pathways in the KO cells, with reduced MET protein levels, decreased TWIST protein expression, and increased SNAIL protein and MALAT1 mRNA levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Rolake O. Alabi, Jose Lora, Arda B. Celen, Thorsten Maretzky, Carl P. Blobel
Summary: The Notch signaling pathway relies on the roles of proteins like ADAM10 and ADAM17 to regulate cell fate, with ADAM17 preferring to process Notch1 in ligand-independent conditions, and ADAM10 preferring to process Notch1 in ligand-dependent conditions. These findings provide new insights into the substrate selectivity mechanisms of ADAM10 and ADAM17 towards Notch1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Joseph Skurski, Garima Dixit, Carl P. Blobel, Priya D. Issuree, Thorsten Maretzky
Summary: A well-controlled innate immune response is characterized by a rapid yet self-limiting inflammatory response, with complex regulatory mechanisms. This study reveals the key role of ADAM17 in regulating the release of TNF, and the signaling of TNFRs in immune cells also plays a regulatory role in TNF expression.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Garima Dixit, Willow Schanz, Benjamin A. Pappas, Thorsten Maretzky
Summary: Metalloproteases ADAM10 and ADAM17 have been identified as differentially regulated FGFR membrane sheddases, playing roles in modulating FGFR signaling during cell migration. Ectodomain shedding can impact the function of ligand-induced FGFR signaling in cell movement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jose Lora, Gisela Weskamp, Thomas M. Li, Thorsten Maretzky, Dorjee T. N. Shola, Sebastien Monette, Stefan F. Lichtenthaler, Theresa T. Lu, Chingwen Yang, Carl P. Blobel
Summary: Mutation of the cytoplasmic domain of ADAM17 in mice using CRISPR-Cas9 technology revealed its pivotal role in regulating ADAM17 levels and function in vivo.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Isabel Pablos, Yoan Machado, Hugo C. Ramos de Jesus, Yasir Mohamud, Reinhild Kappelhoff, Cecilia Lindskog, Marli Vlok, Peter A. Bell, Georgina S. Butler, Peter M. Grin, Quynh T. Cao, Jenny P. Nguyen, Nestor Solis, Srinivas Abbina, Wioletta Rut, John C. Vederas, Laszlo Szekely, Attila Szakos, Marcin Drag, Jayachandran N. Kizhakkedathu, Karen Mossman, Jeremy A. Hirota, Eric Jan, Honglin Luo, Arinjay Banerjee, Christopher M. Overall
Summary: Research on the main viral protease of SARS-CoV-2 and its relationship with human protein substrates has revealed a large group of substrates, accelerating the exploration of pathophysiology and drug design. The study also demonstrates the interactions between 3CL(pro) and the Hippo pathway and other key effector proteins in human cells.
Article
Immunology
Shan-Yu Fung, Henry Y. Lu, Mehul Sharma, Ashish A. Sharma, Aabida Saferali, Alicia Jia, Libin Abraham, Theo Klein, Michael R. Gold, Luigi D. Noterangelo, Christopher M. Overall, Stuart E. Turvey
Summary: NF-kappa B is a crucial transcription factor regulated by LUBAC, which catalyzes linear ubiquitination of target proteins. Research suggests that MALT1-dependent cleavage impacts HOIL1 modulation of NF-kappa B signaling, affecting the intensity of inflammatory responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Sruthi Vijaya Retnakumar, Ramasatyaveni Geesala, Alexis Bretin, Julien Tourneur-Marsille, Eric Ogier-Denis, Thorsten Maretzky, Hang Thi Thu Nguyen, Sylviane Muller
Summary: Inflammatory bowel disease (IBD) is a growing global health problem, and there is currently a lack of safe and targeted medicines for its treatment. This study investigated the potential use of a therapeutic peptide, P140, which corrects autophagy dysfunctions, in three mouse models of colitis. The results showed that P140 treatment attenuated the severity of colitis and corrected the expression of autophagy markers and pro-inflammatory mediators. These findings suggest that the autophagy modulator P140 holds promise for the treatment of IBD.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Multidisciplinary Sciences
Athmane Teghanemt, Priyanjali Pulipati, Kara Misel-Wuchter, Kenneth Day, Matthew S. Yorek, Ren Yi, Henry L. Keen, Christy Au, Thorsten Maretzky, Prajwal Gurung, Dan R. Littman, Priya D. Issuree
Summary: The epigenetic patterns established during thymic T cell development influence the functionality of mature T cells. The study provides evidence that early developmental programming of the Cd4 locus involves DNA demethylation at a specific stimulus-responsive element, allowing long-term maintenance of activator histone H3K4 trimethylation and transcription.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Gilbert S. Omenn, Lydie Lane, Christopher M. Overall, Charles Pineau, Nicolle H. Packer, Ileana M. Cristea, Cecilia Lindskog, Susan T. Weintraub, Sandra Orchard, Michael H. A. Roehrl, Edouard Nice, Siqi Liu, Nuno Bandeira, Yu-Ju Chen, Tiannan Guo, Ruedi Aebersold, Robert L. Moritz, Eric W. Deutsch
Summary: According to the 2022 metrics of the HUPO Human Proteome Project (HPP), protein expression has been detected for 93.2% of the predicted proteins in the human genome. The number of missing proteins has been reduced, indicating experimental progress and reclassification. Proteomics continues to yield significant findings in biological and clinical studies and integrates with other omics platforms.
JOURNAL OF PROTEOME RESEARCH
(2023)
Editorial Material
Biochemical Research Methods
John R. Yates, Ileana M. Cristea, Meng-Qui Dong, Claire E. Eyers, Joshua LaBaer, Jia V. Li, Jeremy K. Nicholson, Christopher M. Overall, Magnus Palmblad, Nikolai Slavov
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Multidisciplinary Sciences
Jina Yun, Simon Hansen, Otto Morris, David T. Madden, Clare Peters Libeu, Arjun J. Kumar, Cameron Wehrfritz, Aaron H. Nile, Yingnan Zhang, Lijuan Zhou, Yuxin Liang, Zora Modrusan, Michelle B. Chen, Christopher C. Overall, David Garfield, Judith Campisi, Birgit Schilling, Rami N. Hannoush, Heinrich Jasper
Summary: Cellular senescence and the senescence-associated secretory phenotype (SASP) play a role in aging and age-related diseases. The inflammation caused by SASP is believed to contribute to tissue dysfunction in aging and diseased animals. Research using intestinal organoids as a model has found that SASP factors released by senescent fibroblasts disturb stem cell activity and differentiation, leading to impaired crypt formation. It has been discovered that the N-terminal domain of Ptk7, which is secreted by senescent cells, activates non-canonical Wnt/Ca2+ signaling through FZD7 in intestinal stem cells (ISCs), disrupting symmetry breaking and stem cell differentiation. This study provides insight into the mechanism by which cellular senescence contributes to tissue dysfunction in aging and disease.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Peter A. Bell, Christopher M. Overall
Summary: Proteolytic processing, the most common post-translational modification, has a significant impact on protein function. By reanalyzing shotgun proteomics datasets, we found evidence of proteolytic processing in COVID-19, which provides valuable insights for studying protease function and virus-host interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Aleksander M. Haack, Christopher M. Overall, Ulrich auf dem Keller
Summary: The extracellular matrix (ECM) is composed of proteins secreted by cells and plays a crucial role in maintaining tissue homeostasis and cellular control. Aberrant signaling through the ECM can lead to various pathological conditions. Therefore, characterizing the components of the ECM and developing novel therapeutics are of great importance.
Article
Biochemistry & Molecular Biology
Peter A. Bell, Sophia Scheuermann, Florian Renner, Christina L. Pan, Henry Y. Lu, Stuart E. Turvey, Frederic Bornancin, Catherine H. Regnier, Christopher M. Overall
Summary: Researchers developed a bioinformatics-led substrate discovery workflow to expand the known substrate repertoire of MALT1. They identified seven new MALT1 substrates using their approach and confirmed their functions in NF-κB regulation.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Correction
Multidisciplinary Sciences
Thorsten Maretzky, David R. McIlwain, Priya Darshinee A. Issuree, Xue Li, Jordi Malapeira, Sadaf Amin, Philipp A. Lang, Tak W. Mak, Carl P. Blobel
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)