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  1. Book: Can precision medicine be personal; Can personalized medicine be precise?

    Ciechanover, Aaron / Brusa, Margherita / Barilan, Y. Michael

    2022  

    Author's details Yechiel Michael Barilan was born and educated in Israel. He is an expert in Internal Medicine and js most recently a senior physician in the Covid-19 Dept. and Emergency Dept. Tel Aviv Medical Centre. He is a full professor in the Tel Aviv University School of Medicine, specializing in ethics and social history of medicine. He is also a member of national and international ethics committees and is an author of over a hundred peer reviewed academic publications. Margherita Brusa earned a PhD in bioethics from the University Complutense of Madrid, and a second PhD in paediatric healthcare planning from the University of Padua. She has served in ethics committees in Spain, USA, and Italy, and led the creation of the first ethics committee in the Palestinian Authority. The focus of her research is bioethics and children. Aaron Ciechanover is an Israeli physician and scientist working currently at the Faculty of Medicine of the Technion-Israel Institute of Technology in Haifa, Israel. He
    Size 352 p.
    Publisher Oxford University Press
    Document type Book
    Note PDA Manuell_14
    Format 137 x 214 x 20
    ISBN 9780198863465 ; 0198863462
    Database PDA

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  2. Article ; Online: Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression.

    Lazar, Ikrame / Livneh, Ido / Ciechanover, Aaron / Fabre, Bertrand

    Cells

    2024  Volume 13, Issue 2

    Abstract: Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes responsible for linking a transfer RNA (tRNA) with its cognate amino acid present in all the kingdoms of life. Besides their aminoacyl-tRNA synthetase activity, it was described that many of these ... ...

    Abstract Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes responsible for linking a transfer RNA (tRNA) with its cognate amino acid present in all the kingdoms of life. Besides their aminoacyl-tRNA synthetase activity, it was described that many of these enzymes can carry out non-canonical functions. They were shown to be involved in important biological processes such as metabolism, immunity, development, angiogenesis and tumorigenesis. In the present work, we provide evidence that tryptophanyl-tRNA synthetase might be involved in a negative feedback loop mitigating the expression of certain interferon-γ-induced genes. Mining the available TCGA and Gtex data, we found that
    MeSH term(s) Humans ; Tryptophan-tRNA Ligase/genetics ; Interferon-gamma/pharmacology ; Feedback ; Melanoma/genetics ; Skin Neoplasms ; Amino Acyl-tRNA Synthetases ; RNA, Transfer ; Gene Expression ; Apolipoprotein L1
    Chemical Substances Tryptophan-tRNA Ligase (EC 6.1.1.2) ; Interferon-gamma (82115-62-6) ; Amino Acyl-tRNA Synthetases (EC 6.1.1.-) ; RNA, Transfer (9014-25-9) ; APOL1 protein, human ; Apolipoprotein L1
    Language English
    Publishing date 2024-01-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells13020180
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Intracellular protein degradation: From a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting.

    Ciechanover, Aaron

    Best practice & research. Clinical haematology

    2017  Volume 30, Issue 4, Page(s) 341–355

    Abstract: Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian ... ...

    Abstract Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis is largely non-lysosomal, but the mechanisms involved remained obscure. The discovery of the ubiquitin-proteasome system resolved the enigma. We now recognize that degradation of intracellular proteins is involved in regulation of a broad array of cellular processes, such as cell cycle and division, regulation of transcription factors, and assurance of the cellular quality control. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of human disease, such as malignancies and neurodegenerative disorders, which led subsequently to an increasing effort to develop mechanism-based drugs.
    MeSH term(s) Animals ; Cell Cycle ; Humans ; Lysosomes/metabolism ; Lysosomes/pathology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neurodegenerative Diseases/therapy ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; Ubiquitin/metabolism
    Chemical Substances Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2017-09-22
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2048027-1
    ISSN 1532-1924 ; 1521-6926
    ISSN (online) 1532-1924
    ISSN 1521-6926
    DOI 10.1016/j.beha.2017.09.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The unravelling of the ubiquitin system.

    Ciechanover, Aaron

    Nature reviews. Molecular cell biology

    2015  Volume 16, Issue 5, Page(s) 322–324

    Abstract: Today, many scientific discoveries are made using a top-down experimental approach. The ubiquitin system was discovered using a 'classic' bottom-up approach to tackle the question: 'how are cellular proteins selectively degraded?' A simple proteolytic ... ...

    Abstract Today, many scientific discoveries are made using a top-down experimental approach. The ubiquitin system was discovered using a 'classic' bottom-up approach to tackle the question: 'how are cellular proteins selectively degraded?' A simple proteolytic assay, which used a crude cell-extract, was all that was required to address this question; it was followed by fractionation and reconstitution experiments to decipher the role of the components in this multi-step process. This 'biochemistry at its best' approach, which was published in a periodical that today would not be regarded as highly visible, provided magnificent findings.
    MeSH term(s) Animals ; Humans ; Lysosomes/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; Reticulocytes/metabolism ; Ubiquitin/chemistry ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligase Complexes/metabolism
    Chemical Substances Ubiquitin ; Ubiquitin-Protein Ligase Complexes (EC 2.3.2.23) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2015
    Publishing country England
    Document type Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/nrm3982
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  5. Article ; Online: A possible non-proteolytic role of ubiquitin conjugation in alleviating the pathology of Huntingtin's aggregation.

    Ziv, Noam E / Ciechanover, Aaron

    Cell death and differentiation

    2020  Volume 28, Issue 2, Page(s) 814–817

    MeSH term(s) Animals ; Humans ; Huntington Disease/metabolism ; Huntington Disease/pathology ; Ubiquitin/metabolism ; Ubiquitination
    Chemical Substances Ubiquitin
    Language English
    Publishing date 2020-09-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225672-9
    ISSN 1476-5403 ; 1350-9047
    ISSN (online) 1476-5403
    ISSN 1350-9047
    DOI 10.1038/s41418-020-00617-7
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  6. Article: The NF-ĸB p50 subunit generated by KPC1-mediated ubiquitination and limited proteasomal processing, suppresses tumor growth.

    Kravtsova-Ivantsiv, Yelena / Goldhirsh, Gilad / Tomuleasa, Ciprian / Pikarsky, Eli / Ciechanover, Aaron

    Cancer cell international

    2023  Volume 23, Issue 1, Page(s) 67

    Abstract: Nuclear factor-ĸB (NF-ĸB) is an important transcriptional regulator of key cellular processes, including cell cycle, immune response, and malignant transformation. We found that the ubiquitin ligase Kip1 ubiquitination-promoting complex subunit 1 (KPC1; ... ...

    Abstract Nuclear factor-ĸB (NF-ĸB) is an important transcriptional regulator of key cellular processes, including cell cycle, immune response, and malignant transformation. We found that the ubiquitin ligase Kip1 ubiquitination-promoting complex subunit 1 (KPC1; also known as Ring finger protein 123 - RNF123) stimulates ubiquitination and limited proteasomal processing of the p105 NF-ĸB precursor to generate p50, the active subunit of the heterodimeric transcription factor. KPC1 binds to the ankyrin repeats' (AR) domain of NF-ĸB p105 via a short binding site of 7 amino acids-968-WILVRLW-974. Though mature NF-ĸB is overexpressed and constitutively active in different tumors, we found that overexpression of the p50 subunit, exerts a strong tumor suppressive effect. Furthermore, excess of KPC1 that stimulates generation of p50 from the p105 precursor, also results in a similar effect. Analysis of transcripts of glioblastoma and breast tumors revealed that excess of p50 stimulates expression of many NF-ĸB-regulated tumor suppressive genes. Using human xenograft tumor models in different immune compromised mice, we demonstrated that the immune system plays a significant role in the tumor suppressive activity of p50:p50 homodimer stimulating the expression of the pro-inflammatory cytokines CCL3, CCL4, and CCL5 in both cultured cells and in the xenografts. Expression of these cytokines leads to recruitment of macrophages and NK cells, which restrict tumor growth. Finally, p50 inhibits the expression of the programmed cell death-ligand 1 (PDL1), establishing an additional level of a strong tumor suppressive response mediated by the immune system.
    Language English
    Publishing date 2023-04-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2091573-1
    ISSN 1475-2867
    ISSN 1475-2867
    DOI 10.1186/s12935-023-02919-5
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  7. Article: Release Our Hostages Now!

    Ashkenazi, Itamar / Beyar, Rafael / Blazer, Shraga / Ciechanover, Aaron / Skorecki, Karl L

    Rambam Maimonides medical journal

    2023  Volume 14, Issue 4

    Language English
    Publishing date 2023-10-29
    Publishing country Israel
    Document type Editorial
    ZDB-ID 2573657-7
    ISSN 2076-9172
    ISSN 2076-9172
    DOI 10.5041/RMMJ.10507
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  8. Article ; Online: A conversation with Aaron Ciechanover. Interview by Ushma S. Neill.

    Ciechanover, Aaron

    The Journal of clinical investigation

    2013  Volume 123, Issue 10, Page(s) 4093–4094

    MeSH term(s) Biochemistry/history ; History, 20th Century ; History, 21st Century ; Israel ; Massachusetts ; Nobel Prize ; Proteolysis
    Language English
    Publishing date 2013-10-01
    Publishing country United States
    Document type Autobiography ; Biography ; Historical Article ; Interview ; Portrait
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI71859
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  9. Article ; Online: Intracellular protein degradation: from a vague idea through the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting.

    Ciechanover, Aaron

    Bioorganic & medicinal chemistry

    2013  Volume 21, Issue 12, Page(s) 3400–3410

    Abstract: Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian ... ...

    Abstract Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis is largely non-lysosomal, but the mechanisms involved remained obscure. The discovery of the ubiquitin-proteasome system resolved the enigma. We now recognize that degradation of intracellular proteins is involved in regulation of a broad array of cellular processes, such as cell cycle and division, regulation of transcription factors, and assurance of the cellular quality control. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of human disease, such as malignancies and neurodegenerative disorders, which led subsequently to an increasing effort to develop mechanism-based drugs.
    MeSH term(s) Animals ; Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/metabolism ; Disease ; Drug Delivery Systems ; Humans ; Lysosomes/chemistry ; Lysosomes/metabolism ; Proteasome Endopeptidase Complex/chemistry ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/chemistry ; Ubiquitin/metabolism
    Chemical Substances Cell Cycle Proteins ; Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2013-06-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2013.01.056
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  10. Article: An interview with Aaron Ciechanover.

    Ciechanover, Aaron

    Trends in biochemical sciences

    2013  Volume 38, Issue 5, Page(s) 219–221

    MeSH term(s) History, 20th Century ; History, 21st Century ; Humans ; Israel ; Proteolysis ; Ubiquitin/history ; Ubiquitin/metabolism
    Chemical Substances Ubiquitin
    Language English
    Publishing date 2013-05
    Publishing country England
    Document type Autobiography ; Biography ; Historical Article ; Interview ; Portraits
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2013.02.007
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