المؤلفون: Gaur, Preksha, Rajendran, Yesheswini, Srivastava, Bhagyashree, Markandey, Manasvini, Fishbain-Yoskovitz, Vered, Mohapatra, Gayatree, Suhail, Aamir, Chaudhary, Shikha, Tyagi, Shaifali, Yadav, Subhash Chandra, Pandey, Amit Kumar, Merbl, Yifat, Bajaj, Avinash, Ahuja, Vineet, Srikanth, Chittur

المساهمون: Department of Biotechnology, Ministry of Science and Technology, India

المصدر: eLife ; volume 12 ; ISSN 2050-084X

الوصف: Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier, coupled with microbial dysbiosis, has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7 KD ) displayed a compromised mucus layer, increased microbial permeability, and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7-dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.

الإتاحة: https://doi.org/10.7554/elife.89776.3Test
https://cdn.elifesciences.org/articles/89776/elife-89776-v1.pdfTest
https://cdn.elifesciences.org/articles/89776/elife-89776-v1.xmlTest
https://elifesciences.org/articles/89776Test

المؤلفون: Levy, Ronen, Regev, Tal Alter, Paes, Wayne, Gumpert, Nofar, Shvefel, Sapir Cohen, Bartok, Osnat, Dayan-Rubinov, Maria, Alon, Michal, Shmueli, Merav D., Levin, Yishai, Merbl, Yifat, Ternette, Nicola, Samuels, Yardena

المساهمون: Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics

مصطلحات موضوعية: Analytical Chemistry, Biochemistry, Molecular Biology

الوصف: Posttranslational spliced peptides (PTSPs) are a unique class of peptides that have been found to be presented by HLA class-I molecules in cancer. Thus far, no consensus has been reached on the proportion of PTSPs in the immunopeptidome, with estimates ranging from 2% to as high as 45% and stirring significant debate. Furthermore, the role of the HLA class-II pathway in PTSP presentation has been studied only in diabetes. Here, we exploit our large-scale cancer peptidomics database and our newly devised pipeline for filtering spliced peptide predictions to identify recurring spliced peptides, both for HLA class-I and class-II complexes. Our results indicate that HLA class-I–spliced peptides account for a low percentage of the immunopeptidome (less than 3.1%) yet are larger in number relative to other types of identified aberrant peptides. Therefore, spliced peptides significantly contribute to the repertoire of presented peptides in cancer cells. In addition, we identified HLA class-II–bound spliced peptides, but to a lower extent (less than 0.5%). The identified spliced peptides include cancer- and immune-associated genes, such as the MITF oncogene, DAPK1 tumor suppressor, and HLA-E, which were validated using synthetic peptides. The potential immunogenicity of the DAPK1- and HLA-E–derived PTSPs was also confirmed. In addition, a reanalysis of our published mouse single-cell clone immunopeptidome dataset showed that most of the spliced peptides were found repeatedly in a large number of the single-cell clones. Establishing a novel search-scheme for the discovery and evaluation of recurring PTSPs among cancer patients may assist in identifying potential novel targets for immunotherapy.

وصف الملف: application/pdf

العلاقة: https://dspace.library.uu.nl/handle/1874/435834Test

الإتاحة: https://dspace.library.uu.nl/handle/1874/435834Test

المؤلفون: Benyair, Ron, Panapakkam Giridharan, Sai Srinivas, Rivero-Ríos, Pilar, Hasegawa, Junya, Bristow, Emily, Eskelinen, Eeva-Liisa, Shmueli, Merav D, Fishbain-Yoskovitz, Vered, Merbl, Yifat, Sharkey, Lisa M, Paulson, Henry L., Hanson, Phyllis I, Patnaik, Samarjit, Al-Ramahi, Ismael, Botas, Juan, Marugan, Juan, Weisman, Lois S.

المصدر: Autophagy Reports ; volume 2, issue 1 ; ISSN 2769-4127

الإتاحة: https://doi.org/10.1080/27694127.2023.2166722Test

المؤلفون: Sheban, Daoud, Shani, Tom, Maor, Roey, Aguilera-Castrejon, Alejandro, Mor, Nofar, Oldak, Bernardo, Shmueli, Merav D., Eisenberg-Lerner, Avital, Bayerl, Jonathan, Hebert, Jakob, Viukov, Sergey, Chen, Guoyun, Kacen, Assaf, Krupalnik, Vladislav, Chugaeva, Valeriya, Tarazi, Shadi, Rodríguez-delaRosa, Alejandra, Zerbib, Mirie, Ulman, Adi, Masarwi, Solaiman, Kupervaser, Meital, Levin, Yishai, Shema, Efrat, David, Yael, Novershtern, Noa, Hanna, Jacob H., Merbl, Yifat

المصدر: Molecular Cell ; volume 82, issue 1, page 106-122.e9 ; ISSN 1097-2765

مصطلحات موضوعية: Cell Biology, Molecular Biology

الإتاحة: https://doi.org/10.1016/j.molcel.2021.11.011Test
https://api.elsevier.com/content/article/PII:S1097276521009904?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1097276521009904?httpAccept=text/plainTest

المؤلفون: Gaur, Preksha, Rajendran, Yesheswini, Srivastava, Bhagyashree, Markandey, Manasvini, Fishbain-Yoskovitz, Vered, Mohapatra, Gayatree, Suhail, Aamir, Chaudhary, Shikha, Tyagi, Shaifali, Yadav, Subhash C, Pandey, Amit K, Merbl, Yifat, Bajaj, Avinash, Ahuja, Vineet, Srikanth, Chittur V

الإتاحة: https://doi.org/10.7554/elife.89776.2.sa3Test

المؤلفون: Shmueli, Merav D., Sheban, Daoud, Eisenberg‐Lerner, Avital, Merbl, Yifat

المساهمون: H2020 Marie Skłodowska-Curie Actions, Israel Science Foundation, H2020 European Research Council

المصدر: The FEBS Journal ; volume 289, issue 12, page 3304-3316 ; ISSN 1742-464X 1742-4658

الوصف: Histones constitute the primary protein building blocks of the chromatin and play key roles in the dynamic control of chromatin compaction and epigenetic regulation. Histones are regulated by intricate mechanisms that alter their functionality and stability, thereby expanding the regulation of chromatin‐transacting processes. As such, histone degradation is tightly regulated to provide spatiotemporal control of cellular histone abundance. While several mechanisms have been implicated in controlling histone stability, here, we discuss proteasome‐dependent degradation of histones and the protein modifications that are associated with it. We then highlight specific cellular and physiological states that are associated with altered histone degradation by cellular proteasomes.

الإتاحة: https://doi.org/10.1111/febs.15903Test

المؤلفون: Eisenberg-Lerner, Avital, Benyair, Ron, Hizkiahou, Noa, Nudel, Neta, Maor, Roey, Kramer, Matthias P., Shmueli, Merav D., Zigdon, Inbal, Cherniavsky Lev, Marina, Ulman, Adi, Sagiv, Jitka Yehudith, Dayan, Molly, Dassa, Bareket, Rosenwald, Mercedes, Shachar, Idit, Li, Jie, Wang, Yanzhuang, Dezorella, Nili, Khan, Suman, Porat, Ziv, Shimoni, Eyal, Avinoam, Ori, Merbl, Yifat

المساهمون: Israel Science Foundation, Council for Higher Education of Israel | Israeli Centers for Research Excellence

المصدر: Nature Communications ; volume 11, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis. Perturbations in Golgi structure are associated with numerous disorders from neurodegeneration to cancer. However, whether and how dispersal of the Golgi apparatus is actively regulated under stress, and the consequences of Golgi dispersal, remain unknown. Here we demonstrate that 26S proteasomes are associated with the cytosolic surface of Golgi membranes to facilitate Golgi Apparatus-Related Degradation (GARD) and degradation of GM130 in response to Golgi stress. The degradation of GM130 is dependent on p97/VCP and 26S proteasomes, and required for Golgi dispersal. Finally, we show that perturbation of Golgi homeostasis induces cell death of multiple myeloma in vitro and in vivo, offering a therapeutic strategy for this malignancy. Taken together, this work reveals a mechanism of Golgi-localized proteasomal degradation, providing a functional link between proteostasis control and Golgi architecture, which may be critical in various secretion-related pathologies.

الإتاحة: https://doi.org/10.1038/s41467-019-14038-9Test
https://www.nature.com/articles/s41467-019-14038-9.pdfTest
https://www.nature.com/articles/s41467-019-14038-9Test

المؤلفون: Marmor-Kollet, Hagai, Siany, Aviad, Kedersha, Nancy, Knafo, Naama, Rivkin, Natalia, Danino, Yehuda M., Moens, Thomas G., Olender, Tsviya, Sheban, Daoud, Cohen, Nir, Dadosh, Tali, Addadi, Yoseph, Ravid, Revital, Eitan, Chen, Toth Cohen, Beata, Hofmann, Sarah, Riggs, Claire L., Advani, Vivek M., Higginbottom, Adrian, Cooper-Knock, Johnathan, Hanna, Jacob H., Merbl, Yifat, Van Den Bosch, Ludo, Anderson, Paul, Ivanov, Pavel, Geiger, Tamar, Hornstein, Eran

المساهمون: Horizon 2020, Israel Science Foundation, National Institutes of Health, ALS Therapy Alliance, European Research Council, Fondation Thierry Latran, Target ALS, Minerva Foundation, Motor Neurone Disease Association

المصدر: Molecular Cell ; volume 80, issue 5, page 876-891.e6 ; ISSN 1097-2765

مصطلحات موضوعية: Cell Biology, Molecular Biology

الإتاحة: https://doi.org/10.1016/j.molcel.2020.10.032Test
https://api.elsevier.com/content/article/PII:S1097276520307395?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1097276520307395?httpAccept=text/plainTest

المؤلفون: Quintana, Francisco J., Hagedorn, Peter H., Elizur, Gad, Merbl, Yifat, Domany, Eytan, Cohen, Irun R.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2004 Oct 01. 101, 14615-14621.

الوصول الحر: https://www.jstor.org/stable/3373496Test

المؤلفون: Kacen, Assaf, Javitt, Aaron, Kramer, Matthias P, Morgenstern, David, Tsaban, Tomer, Shmueli, Merav D, Teo, Guo Ci, da Veiga Leprevost, Felipe, Barnea, Eilon, Yu, Fengchao, Admon, Arie, Eisenbach, Lea, Samuels, Yardena, Schueler-Furman, Ora, Levin, Yishai, Nesvizhskii, Alexey I, Merbl, Yifat

المصدر: Nat Biotechnol ; ISSN:1546-1696 ; Volume:41 ; Issue:2

الوصف: Post-translational modification (PTM) of antigens provides an additional source of specificities targeted by immune responses to tumors or pathogens, but identifying antigen PTMs and assessing their role in shaping the immunopeptidome is challenging. Here we describe the Protein Modification Integrated Search Engine (PROMISE), an antigen discovery pipeline that enables the analysis of 29 different PTM combinations from multiple clinical cohorts and cell lines. We expanded the antigen landscape, uncovering human leukocyte antigen class I binding motifs defined by specific PTMs with haplotype-specific binding preferences and revealing disease-specific modified targets, including thousands of new cancer-specific antigens that can be shared between patients and across cancer types. Furthermore, we uncovered a subset of modified peptides that are specific to cancer tissue and driven by post-translational changes that occurred in the tumor proteome. Our findings highlight principles of PTM-driven antigenicity, which may have broad implications for T cell-mediated therapies in cancer and beyond.

العلاقة: https://doi.org/10.1038/s41587-022-01464-2Test; https://pubmed.ncbi.nlm.nih.gov/36203013Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197725Test/

الإتاحة: https://doi.org/10.1038/s41587-022-01464-2Test
https://pubmed.ncbi.nlm.nih.gov/36203013Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197725Test/