Article
Oncology
Corey M. Gill, Joshua Loewenstern, John W. Rutland, Hanane Arib, Margaret Pain, Melissa Umphlett, Yayoi Kinoshita, Russell B. McBride, Joshua Bederson, Michael Donovan, Robert Sebra, Mary Fowkes, Raj K. Shrivastava
Summary: ARID1A mutations occur with similar frequency between low and high-grade meningiomas, but ARID1A mutations are independently prognostic of worse prognosis beyond clinical and histopathologic features.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Plant Sciences
Elzbieta Sarnowska, Szymon Kubala, Pawel Cwiek, Sebastian Sacharowski, Paulina Oksinska, Jaroslaw Steciuk, Magdalena Zaborowska, Jakub M. Szurmak, Roman Dubianski, Anna Maassen, Malgorzata Stachowiak, Bruno Huettel, Monika Ciesla, Klaudia Nowicka, Anna T. Rolicka, Saleh Alseekh, Ernest Bucior, Rainer Franzen, Anna Skoneczna, Malgorzata A. Domagalska, Samija Amar, Mohammad-Reza Hajirezaei, Janusz A. Siedlecki, Alisdair R. Fernie, Seth J. Davis, Tomasz J. Sarnowski
Summary: The Arabidopsis ERECTA family of leucine-rich repeat receptor-like kinases (LRR-RLKs) controls various developmental processes and interacts with the SWI/SNF chromatin remodeling complex. The er/erl1/erl2 mutant shows impaired gibberellin signaling, decreased SWI3B protein level, and altered chromatin structure. ERf-SWI/SNF CRC interaction plays an important role in transcriptional control of gibberellin receptors.
Review
Oncology
Motoyuki Tsuda, Akihisa Fukuda, Munenori Kawai, Osamu Araki, Hiroshi Seno
Summary: ATP-dependent chromatin remodeling complexes, particularly the SWI/SNF complex, play crucial roles in regulating gene expression and have been found to be mutated in a significant percentage of human cancers, including pancreatic ductal adenocarcinoma (PDA). Research has shown that the subunits of the SWI/SNF complex in PDA have context-dependent roles in tumorigenesis, with potential therapeutic implications for targeting their oncogenic or tumor-suppressive properties in PDA. Further understanding of the precise roles of SWI/SNF complex subunits in PDA is necessary for the development of novel therapeutic strategies against this lethal type of cancer.
Review
Biochemistry & Molecular Biology
Ji-Yun Shang, Xin-Jian He
Summary: Adenosine triphosphate-dependent chromatin remodeling complexes play a crucial role in transcription, DNA replication, and genome stability regulation in eukaryotes. However, the study of chromatin remodeling complexes in plants lags behind yeast and animals. Recent research has identified and characterized the composition and function of chromatin remodeling enzymes in Arabidopsis, providing a foundation for further investigation into the molecular mechanisms.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2022)
Article
Cell Biology
Xin Li, Shanshan Wang, Xilan Yu, Shanshan Li
Summary: Autophagy is a catabolic process that maintains homeostasis and is involved in cell differentiation and development. The chromatin remodeling complex INO80 and histone variant H2A.Z have been identified as new regulators of autophagy, and the histone deacetylase Rpd3L complex plays a role in repressing autophagy by deacetylating Ino80 and H2A.Z. These findings highlight the importance of chromatin remodelers and histone variants in regulating autophagy in response to nutrient availability.
Article
Biochemistry & Molecular Biology
N. V. Soshnikova, E. V. Tatarskiy, V. V. Tatarskiy, N. S. Klimenko, A. A. Shtil, M. A. Nikiforov, S. G. Georgieva
Summary: The PBAF complex, with its PHF10 subunit, plays a crucial role in transcriptional regulation and is associated with disease progression in melanoma. The interaction between PHF10 and MYC enhances MYC's activation of genes involved in cell cycle progression. Depletion of PHF10 or MYC leads to G1 accumulation and a senescence-like phenotype in melanoma cells.
Review
Biochemistry & Molecular Biology
Ieva Vaicekauskaite, Rasa Sabaliauskaite, Juozas Rimantas Lazutka, Sonata Jarmalaite
Summary: Ovarian cancer is the fifth leading cause of women's death from cancers, with high mortality rate due to late presence and lack of modern diagnostic tools. It is a highly heterogeneous disease, leading to early treatment failure. Exploring molecular mechanisms of ovarian cancer can enhance our understanding and provide new treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Corinna Lieleg, Ana Novacic, Sanja Musladin, Andrea Schmid, Goezde Gueclueler Akpinar, Slobodan Barbaric, Philipp Korber
Summary: Chromatin remodeling by ATP-dependent enzymes is crucial for genomic processes. The recruitment of remodelers, such as the SWI/SNF complex, in the removal of nucleosomes in yeast PHO gene induction is specific and may affect the outcome of remodeling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Mingxuan Li, Yutao Shen, Yujia Xiong, Shuai Wang, Chuzhong Li, Jiwei Bai, Yazhuo Zhang
Summary: The study revealed that SMARCB1 functions as a tumor suppressor in chordoma by inhibiting the malignant phenotype of chordoma cells. SMARCB1 inhibits autophagy through direct binding to the ATG5 promoter, leading to decreased ATG5 expression and impaired autophagy. High ATG5 expression is associated with adverse outcomes in recurrent chordoma patients.
CELL PROLIFERATION
(2021)
Article
Cell Biology
Iris E. Ertl, Robert Brettner, Hannah Kronabitter, Thomas Mohr, Sophia Derdak, Markus Jeitler, Martin Bilban, Nathalie Garstka, Shahrokh F. Shariat
Summary: Previous studies have shown that chromatin-remodelling SWI/SNF complexes are involved in prostate cancer development, with both tumor suppressor and oncogenic activities. Our study on SMARCD family members revealed their role in regulating hormone-dependent genes and their involvement in castration-resistance. We also found that SMARCD proteins play a role in cellular processes like cellular morphology and cytokinesis. Overall, our findings highlight the important and paradoxical role of SMARCD proteins in prostate carcinogenesis.
Article
Cell Biology
Chiyang Li, Tong Wang, Junwei Gu, Songtao Qi, Junjie Li, Lei Chen, Hang Wu, Linyong Shi, Chong Song, Hong Li, Liwen Zhu, Yuntao Lu, Qiang Zhou
Summary: This study reveals a unique function of SMARCC2 in inhibiting glioblastoma progression by targeting the DKK1 signaling axis. SMARCC2 negatively regulates DKK1 transcription through chromatin remodeling, resulting in suppressed proliferation of glioblastoma cells.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Javeed Ahmad Bhat, Angela J. Balliano, Jeffrey J. Hayes
Summary: Chromatin remodeling enzymes use energy to alter the structure of nucleosomes, facilitating DNA access. This study reveals that the RSC complex requires access to the trailing protein surface of the nucleosome for mobilization, indicating a mechanism for regulating DNA sequences.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
Yuan Tian, Rachel K. Smith-Bolton
Summary: Chromatin modifiers are crucial for controlling gene expression during tissue regeneration in fruit fly larvae. Two SWI/SNF chromatin-remodeling complexes, PBAP and BAP, play distinct roles in regulating regenerative growth and developmental timing, as well as cell fate and patterning during the regeneration process.
Review
Oncology
Jaren Mullen, Shumei Kato, Jason K. Sicklick, Razelle Kurzrock
Summary: Mutations in ARID1A, a subunit gene of the SWI/SNF chromatin remodeling complex, are common in various cancers and play a crucial role in regulating gene expression related to oncogenesis and tumor suppression. Targeting ARID1A-altered cancers may involve a combination of immune checkpoint blockade and inhibitors of various pathways.ARID1A alterations may also mediate resistance to specific chemotherapies and hormone therapies.
CANCER TREATMENT REVIEWS
(2021)
Article
Biology
Jiyoon Beon, Sungwook Han, Hyeokjun Yang, Seung Eun Park, Kwangbeom Hyun, Song-Yi Lee, Hyun-Woo Rhee, Jeong Kon Seo, Jaehoon Kim, Seyun Kim, Daeyoup Lee
Summary: Inositol polyphosphate multikinase (IPMK) interacts with the chromatin remodeling complex SWI/SNF and regulates its function in mouse embryonic stem cells, contributing to transcription and differentiation.
Article
Biochemical Research Methods
Soumya Mukherjee, Andris Jankevics, Florian Busch, Markus Lubeck, Yang Zou, Gary Kruppa, Albert J. R. Heck, Richard A. Scheltema, Karli R. Reiding
Summary: Ion mobility enables spatial separation of ions in the gas phase, providing information about their size. The timsTOF Pro device can physically separate N-glycopeptides from nonmodified peptides and produce high-quality fragmentation spectra. This method allows for the effective selection of analytes of interest based on the clear cluster in the mobiologram formed by the glycan moieties enlarging the size of glycopeptides.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Biochemical Research Methods
Wouter van Bergen, Johannes F. Hevler, Wei Wu, Marc P. Baggelaar, Albert J. R. Heck
Summary: Most drugs target proteins, and determining the exact drug binding sites on proteins is crucial for understanding their effects. A strategy called PhosID-ABPP was developed to identify drug binding sites using immobilized metal-affinity chromatography and phosphonate affinity tags. This method successfully identified over 500 unique binding sites of the drug PF-06672131. PhosID-ABPP also revealed differences in binding sites between intact cells and cell lysates, and captured a previously elusive binding site on the epidermal growth factor receptor.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Review
Chemistry, Multidisciplinary
Evolene Desligniere, Amber Rolland, Eduard H. T. M. Ebberink, Victor Yin, Albert J. R. Heck
Summary: Native mass spectrometry is widely used for determining the mass of intact proteins and their biomolecular assemblies. However, it can be challenging for heterogeneous protein complexes. In 2012, an Orbitrap-based mass analyzer with extended mass range was introduced, enabling high-resolution mass spectra of large protein assemblies and single ion measurements. This led to the development of single-molecule Orbitrap-based charge detection mass spectrometry in 2020, which has opened doors for innovative research in various systems.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Gunasekaran Subramaniam, Katharina Schleicher, Duangnapa Kovanich, Anna Zerio, Milda Folkmanaite, Ying-Chi Chao, Nicoletta C. Surdo, Andreas Koschinski, Jianshu Hu, Arjen Scholten, Albert J. R. Heck, Maria Ercu, Anastasiia Sholokh, Kyung Chan Park, Enno Klussmann, Viviana Meraviglia, Milena Bellin, Sara Zanivan, Svenja Hester, Shabaz Mohammed, Manuela Zaccolo
Summary: In this study, previously unrecognized cAMP nanodomains associated with beta-adrenergic stimulation were identified using an integrated phosphoproteomics approach and network analysis. The composition and function of one of these nanodomains were validated. The findings reveal a mechanism that explains the negative long-term clinical outcome observed in patients with heart failure treated with PDE3 inhibitors.
CIRCULATION RESEARCH
(2023)
Article
Biochemical Research Methods
Shelley Jager, Dario A. T. Cramer, Albert J. R. Heck
Summary: Alpha-1-antitrypsin (A1AT) has been suggested as a potential biomarker for distinguishing healthy and diseased individuals. However, the variability of the SERPINA1 gene in the general population may affect A1AT expression and serum protein levels, which are often overlooked in proteomics studies. This study found significant differences in allele-specific protein serum levels of A1AT among heterozygous donors, suggesting the importance of considering these factors when analyzing A1AT as a potential serum biomarker.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Johannes F. Hevler, Pascal Albanese, Alfredo Cabrera-Orefice, Alisa Potter, Andris Jankevics, Jelena Misic, Richard A. Scheltema, Ulrich Brandt, Susanne Arnold, Albert J. R. Heck
Summary: The tricarboxylic acid cycle is a central pathway for energy production in eukaryotic cells and plays a key role in aerobic respiration across all life kingdoms. The 2-oxoglutarate dehydrogenase complex (OGDHC) is a crucial enzyme in this cycle, generating NADH by oxidatively decarboxylating 2-oxoglutarate to succinyl-CoA. We provide evidence that MRPS36 is an important component of eukaryotic OGDHC, supported by cross-linking mass spectrometry data and phylogenetic analyses. We propose that MRPS36 evolved as an E3 adaptor protein, functionally replacing the peripheral subunit-binding domain (PSBD) in eukaryotic E2o.
Article
Andrology
Min Zhang, Riccardo Zenezini Chiozzi, Elizabeth G. Bromfield, Albert J. R. Heck, J. Bernd Helms, Bart M. Gadella
Summary: This study aimed to identify the interacting partners of CRISP2. The interactions of these binding partners were investigated under different conditions. The results suggest that CRISP2 may act as a scaffold for protein complex formation and dissociation to ensure the correct positioning of proteins required for the acrosome reaction and zona pellucida penetration.
Article
Biology
Leire Aguinagalde Salazar, Maurits A. den Boer, Suzanne M. Castenmiller, Seline A. Zwarthoff, Carla de Haas, Piet C. Aerts, Frank J. Beurskens, Janine Schuurman, Albert J. R. Heck, Kok van Kessel, Suzan H. M. Rooijakkers
Summary: In this study, it is found that by modifying the structure of monoclonal antibodies (mAbs), the immune protection and bactericidal effect against Streptococcus pneumoniae can be improved. The modified mAbs effectively activate the complement system and recruit complement component C1 for bacterial clearance, enhancing the antibacterial activity against various serotypes of pneumococci. This study provides an important proof of concept for the future development of antibody therapies against encapsulated bacteria.
Article
Biotechnology & Applied Microbiology
Yen-Hsi Chen, Weihua Tian, Makiko Yasuda, Zilu Ye, Ming Song, Ulla Mandel, Claus Kristensen, Lorenzo Povolo, Andre R. A. Marques, Tomislav Caval, Albert J. R. Heck, Julio Lopes Sampaio, Ludger Johannes, Takahiro Tsukimura, Robert Desnick, Sergey Y. Y. Vakhrushev, Zhang Yang, Henrik Clausen
Summary: Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due to short circulation times and suboptimal biodistribution of the therapeutic enzymes. Researchers have engineered Chinese hamster ovary (CHO) cells to produce glycoengineered enzymes, which have improved circulation time and biodistribution. This glycoengineering approach, known as Long-Acting-GlycoDesign (LAGD), may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Oncology
Beiping Miao, Zhaoqing Hu, Riccardo Mezzadra, Lotte Hoeijmakers, Astrid Fauster, Shangce Du, Zhi Yang, Melanie Sator-Schmitt, Helena Engel, Xueshen Li, Caroline Broderick, Guangzhi Jin, Raquel Gomez-Eerland, Lisette Rozeman, Xin Lei, Hitoshi Matsuo, Chen Yang, Ingrid Hofland, Dennis Peters, Annegien Broeks, Elke Laport, Annika Fitz, Xiyue Zhao, Mohamed A. A. Mahmoud, Xiujian Ma, Sandrine Sander, Hai-kun Liu, Guoliang Cui, Yu Gan, Wei Wu, Yanling Xiao, Albert J. R. Heck, Wenxian Guan, Scott W. Lowe, Hugo M. Horlings, Cun Wang, Thijn R. Brummelkamp, Christian U. Blank, Ton N. M. Schumacher, Chong Sun
Summary: The dysregulation of immune checkpoint molecules allows cancer cells to escape immune destruction. CD58, an important costimulatory ligand, is found to be positively regulated by CMTM6, which also interacts with PD-L1. The presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and the response to PD-L1-PD-1 blockade.
Article
Cell Biology
Dusanka Milenkovic, Jelena Misic, Johannes F. Hevler, Thibaut Molinie, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J. R. Heck, Judy Hirst, Nils-Goran Larsson
Summary: The mammalian respiratory chain complexes CI, CIII2, and CIV form a stable assembly called the respirasome, which is critical for cellular bioenergetics. By studying knockin mice with decreased levels of respirasomes, researchers found that high levels of respirasomes are dispensable for maintaining bioenergetics and physiology in mice. However, the alternate functions of respirasomes, such as regulating protein stability and preventing age-associated protein aggregation, need further investigation.
Article
Biochemical Research Methods
Johannes F. Hevler, Albert J. R. Heck
Summary: Mitochondria, packed with proteins, play important roles in various cellular processes. While many mitochondrial protein complexes have been identified, some protein-protein interactions remain elusive. Cross-linking mass spectrometry (XL-MS) has proven to be a valuable tool for the in-depth characterization of these interactions. In this article, experimental strategies for the analysis of proteome-wide protein-protein interactions in mitochondria using XL-MS are highlighted, along with recent technological advances that can further enhance the in situ characterization of these interactions.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Oncology
Marjolein C. Stip, Mitchell Evers, Maaike Nederend, Chilam Chan, Karli R. Reiding, Mirjam J. Damen, Albert J. R. Heck, Sofia Koustoulidou, Ruud Ramakers, Gerard C. Krijger, Remmert de Roos, Edouard Souteyrand, Annelisa M. Cornel, Miranda P. Dierselhuis, Marco Jansen, Mark de Boer, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen, Friederike Meyer-Wentrup
Summary: Researchers engineered an antibody called IgA3.0 ch14.18, which shows promise as a new therapy for neuroblastoma. The antibody has a longer half-life, increased protein stability, and potent tumor-killing abilities.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Inge Gazi, Karli R. Reiding, Andre Groeneveld, Jan Bastiaans, Thom Huppertz, Albert J. R. Heck
Summary: We monitored the changes in bovine milk IgG over a 28-day period after calving, finding that IgG accounts for over 50% of protein content in colostrum but less than 3% in mature milk. The N-glycosylation profile of bovine milk IgG was found to be highly heterogeneous with over 40 glycoforms, and this profile changed significantly during lactation. We also identified the presence of IgG3 subtype in bovine milk, alongside IgG1 and IgG2. These findings are important for understanding calf's immune development and the nutritional value of bovine milk.
Article
Immunology
Kelly A. Dingess, Max Hoek, Danique M. H. van Rijswijk, Sem Tamara, Maurits A. den Boer, Tim Veth, Mirjam J. A. Damen, Arjan Barendregt, Michelle Romijn, Hannah G. Juncker, Britt J. van Keulen, Gestur Vidarsson, Johannes B. van Goudoever, Albert Bondt, Albert J. R. Heck
Summary: The most abundant immunoglobulin in the human body is IgA and it is found in high concentrations in mucosal lining and biofluids like milk. The structure and clonal repertoire of IgA1-containing molecular assemblies were analyzed using mass spectrometry-based approach in serum and milk from three donors. The results showed that serum IgA1 consists of two distinct structural populations, monomeric IgA1 and dimeric J-chain coupled IgA1, while IgA1 in milk is present only as secretory IgA (SIgA) with various assemblies. The IgA1-Fab repertoires in serum and milk were also found to be different.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
