Article
Biochemical Research Methods
Anna M. Kip, Juan Manuel Valverde, Maarten Altelaar, Ron M. A. Heeren, Inca H. R. Hundscheid, Cornelis H. C. Dejong, Steven W. M. Olde Damink, Benjamin Balluff, Kaatje Lenaerts
Summary: This study investigated the proteome and phosphoproteome changes in the human intestine during ischemia-reperfusion using LC-MS/MS and MSI techniques. The findings revealed alterations in proteins related to intestinal absorption, innate immunity, and extracellular matrix organization, as well as the activity of MAPK and CDK families during IR. The study highlights the importance of complementary use of different MS methodologies in understanding molecular changes during IR.
JOURNAL OF PROTEOME RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Thom M. Molenaar, Fred van Leeuwen
Summary: Histone modifying enzymes have important roles in cellular processes and disease. SETD2, for example, methylates histone H3 on lysine 36 (H3K36) during transcription and also methylates non-histone substrates. Understanding the multiple roles of SETD2 is crucial for understanding its role in disease, particularly in cancer where it is frequently inactivated.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Stine Kjaer Morthorst, Camilla Nielsen, Pietro Farinelli, Zeinab Anvarian, Christina Birgitte R. Rasmussen, Andrea Serra-Marques, Ilya Grigoriev, Maarten Altelaar, Nicoline Furstenberg, Alexander Ludwig, Anna Akhmanova, Soren Tvorup Christensen, Lotte Bang Pedersen
Summary: A new interactor of KIF13B, Ap80, has been identified, which promotes the binding of PALS1 to KIF13B and regulates ciliary length, composition and signaling.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Hanneke Vlaming, Claudia A. Mimoso, Andrew R. Field, Benjamin J. E. Martin, Karen Adelman
Summary: This study reveals the importance of transcribed sequence in dictating gene output, with higher AT content in non-coding RNAs leading to RNAPII termination. Additionally, 5' splice sites can autonomously stimulate transcription.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Susanne G. van der Grein, Kyra A. Y. Defourny, Huib H. Rabouw, Soenita S. Goerdayal, Martijn J. C. van Herwijnen, Richard W. Wubbolts, Maarten Altelaar, Frank J. M. van Kuppeveld, Esther N. M. Nolte-'t Hoen
Summary: This article investigates the role of the Leader protein in the non-lytic release of encephalomyocarditis virus (EMCV) through extracellular vesicles. The study reveals that the Leader protein promotes the release of virus particles enclosed in extracellular vesicles, and this process may involve secretory autophagy.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Thom M. Molenaar, Muddassir Malik, Joana Silva, Ning Qing Liu, Judith H. Haarhuis, Christina Ambrosi, Eliza Mari Kwesi-Maliepaard, Tibor van Welsem, Tuncay Baubec, William J. Faller, Fred van Leeuwen
Summary: Cell size is tightly regulated and changes in cell size are frequently observed in cancer. In this study, we found that SETD2, a lysine methyltransferase protein, plays a role in regulating cell size by negatively regulating global protein synthesis rates. Overexpression of the H3K36 demethylase KDM4A or the oncohistone H3.3K36M also led to an increase in cell size, suggesting the importance of H3K36 methylation in cell size regulation.
JOURNAL OF CELL SCIENCE
(2022)
Article
Oncology
Federica Fabro, Nynke M. Kannegieter, Erik L. de Graaf, Karla Queiroz, Martine L. M. Lamfers, Anna Ressa, Sieger Leenstra
Summary: Glioblastoma is the most deadly brain cancer with poor response to treatment. In this study, 2D and 3D models were used to investigate the effects of small protein kinase inhibitors on patient-derived glioblastoma. The results showed inter-patient variability in drug response, with the ErbB signaling pathway playing a role. It was also observed that the choice of model influenced the analysis of kinases. A new resistance mechanism derived from imatinib treatment was identified in one sample.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Olga S. Blomberg, Lorenzo Spagnuolo, Hannah Garner, Leonie Voorwerk, Olga I. Isaeva, Ewald van Dyk, Noor Bakker, Myriam Chalabi, Chris Klaver, Maxime Duijst, Kelly Kersten, Marieke Bruggemann, Dorien Pastoors, Cheei-Sing Hau, Kim Vrijland, Elisabeth A. M. Raeven, Daphne Kaldenbach, Kevin Kos, Inna S. Afonina, Paulien Kaptein, Louisa Hoes, Willemijn S. M. E. Theelen, Paul Baas, Emile E. Voest, Rudi Beyaert, Daniela S. Thommen, Lodewyk F. A. Wessels, Karin E. de Visser, Marleen Kok
Summary: Immune checkpoint blockade (ICB) has revolutionized cancer therapy by promoting effective immune responses through the activation of CD4(+) T cells and the recruitment of eosinophils. This study demonstrates the critical role of eosinophils in ICB response and provides proof-of-principle for enhancing ICB efficacy through eosinophil engagement. Mechanistically, ICB increases IL-5 production, stimulating elevated eosinophil production and systemic eosinophil expansion.
Article
Cell Biology
Lisa Willemsen, Koen H. M. Prange, Annette E. Neele, Cindy P. A. A. Van Roomen, Marion Gijbels, Guillermo R. Griffith, Myrthe Den Toom, Linda Beckers, Ricky Siebeler, Nathanael J. Spann, Hung-Jen Chen, Laura A. Bosmans, Andrej Gorbatenko, Suzanne Van Wouw, Noam Zelcer, Heinz Jacobs, Fred Van Leeuwen, Menno P. J. De Winther
Summary: This study reveals the crucial role of DOT1L in macrophages, showing its direct regulation of macrophage function through lipid regulatory pathways and inflammatory responses. DOT1L inhibition leads to macrophage hyperactivation and disruption of lipid metabolism, which have implications for the development of inflammatory diseases.
Article
Genetics & Heredity
Eliza Mari Kwesi-Maliepaard, Muddassir Malik, Tibor van Welsem, Remco van Doorn, Maarten H. Vermeer, Hanneke Vlaming, Heinz Jacobs, Fred van Leeuwen
Summary: The therapeutic effect of commonly used pan-HDAC inhibitors in CTCL cells may rely on downstream effects that are unrelated to the regulation of DOT1L.
FRONTIERS IN GENETICS
(2022)
Article
Chemistry, Analytical
Fujia Wang, Tim Veth, Marije Kuipers, Maarten Altelaar, Kelly E. Stecker
Summary: A successful mass spectrometry-based phosphoproteomics analysis relies on effective sample preparation strategies. The performance of the S-Trap protocol for phosphoproteomics studies is unclear, and the addition of phosphoric acid (PA) in the existing protocol is detrimental to downstream phosphopeptide enrichment. This study systematically evaluates the performance of the S-Trap digestion for proteomics and phosphoproteomics, and demonstrates that an optimized S-Trap approach, with trifluoroacetic acid substituted for PA, is a simple and effective method for phosphoproteomics sample preparation.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Melina Blanco, Laila El Khattabi, Clara Gobe, Marion Crespo, Manon Coulee, Alberto de la Iglesia, Come Ialy-Radio, Clementine Lapoujade, Maelle Givelet, Marion Delessard, Ivan Seller-Corona, Kosuke Yamaguchi, Nadege Vernet, Fred Van Leeuwen, Alban Lermine, Yuki Okada, Romain Daveau, Rafael Oliva, Pierre Fouchet, Ahmed Ziyyat, Delphine Pflieger, Julie Cocquet
Summary: In this study, it is found that the H3K79-methyltransferase DOT1L plays a crucial role in spermatid chromatin remodeling and gene expression regulation. The knockout of the Dot1l gene in mice resulted in less compact chromatin structure and abnormal content in spermatozoa, including the presence of transition proteins, immature protamine 2 forms, and higher levels of histones. Additionally, the Dot1l knockout also caused less compact heads and decreased motility in spermatozoa, leading to impaired fertility.
Article
Biochemistry & Molecular Biology
Ineke Brouwer, Emma Kerklingh, Fred van Leeuwen, Tineke L. Lenstra
Summary: Using single-molecule live-cell imaging, Brouwer et al. investigate how the remodeling of promoter nucleosomes regulates transcriptional bursting. They find that at the Gal4 binding sites, RSC and Gal4 binding synergistically facilitate each burst. In contrast, nucleosome remodeling at the TATA box controls only the first burst upon galactose induction. The results reveal the importance of promoter nucleosome remodeling in regulating the kinetics of transcription.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Donna O. Debets, Kelly E. Stecker, Anastasia Piskopou, Marte C. Liefaard, Jelle Wesseling, Gabe S. Sonke, Esther H. Lips, Maarten Altelaar
Summary: This study performs (phospho)proteomics analysis of pre-treatment HER2+ needle biopsies of early-stage invasive breast cancer to identify molecular signatures predictive of treatment response. The study finds that accurate quantification of the estrogen receptor (ER) and HER2 biomarkers, along with the assessment of associated biological features, can improve treatment outcome prediction. Additionally, the study identifies cellular mechanisms that potentially precondition tumors to resist therapy.
CELL REPORTS MEDICINE
(2023)
Article
Immunology
Erik L. de Graaf, Mads Delbo Larsen, Nieke van der Bolt, Remco Visser, Onno J. H. M. Verhagen, Agnes L. Hipgrave Ederveen, Carolien A. M. Koeleman, C. Ellen van der Schoot, Manfred Wuhrer, Gestur Vidarsson
Summary: This study evaluates whether clonally related B cells share similar glycosylation patterns in their secreted IgG, revealing highly diverse glycosylation patterns and indicating that fucosylation level is regulated at the single-clone level.
