دورية أكاديمية
أعرض في EDS

The structure, binding and function of a Notch transcription complex involving RBPJ and the epigenetic reader protein L3MBTL3.

التفاصيل البيبلوغرافية
العنوان: The structure, binding and function of a Notch transcription complex involving RBPJ and the epigenetic reader protein L3MBTL3.
المؤلفون: Hall D; University of Cincinnati College of Medicine, Department of Molecular Genetics, Biochemistry and Microbiology, Cincinnati, OH, USA., Giaimo BD; Institute of Biochemistry, University of Giessen, 35392 Giessen, Germany., Park SS; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Hemmer W; University Medical Center Ulm, Center for Internal Medicine, Department of Internal Medicine 1, Albert-Einstein-Allee 23, 89081Ulm, Germany., Friedrich T; Institute of Biochemistry, University of Giessen, 35392 Giessen, Germany., Ferrante F; Institute of Biochemistry, University of Giessen, 35392 Giessen, Germany., Bartkuhn M; Biomedical Informatics and Systems Medicine, University of Giessen, 35392 Giessen, Germany., Yuan Z; University of Cincinnati College of Medicine, Department of Molecular Genetics, Biochemistry and Microbiology, Cincinnati, OH, USA., Oswald F; University Medical Center Ulm, Center for Internal Medicine, Department of Internal Medicine 1, Albert-Einstein-Allee 23, 89081Ulm, Germany., Borggrefe T; Institute of Biochemistry, University of Giessen, 35392 Giessen, Germany., Rual JF; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Kovall RA; University of Cincinnati College of Medicine, Department of Molecular Genetics, Biochemistry and Microbiology, Cincinnati, OH, USA.
المصدر: Nucleic acids research [Nucleic Acids Res] 2022 Dec 09; Vol. 50 (22), pp. 13083-13099.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: DNA-Binding Proteins*/metabolism , Gene Expression Regulation* , Immunoglobulin J Recombination Signal Sequence-Binding Protein*/genetics , Immunoglobulin J Recombination Signal Sequence-Binding Protein*/metabolism, Animals ; Humans ; Epigenesis, Genetic ; Histone Demethylases/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; LIM Domain Proteins/metabolism ; Muscle Proteins/genetics ; Protein Binding ; Receptors, Notch/genetics ; Receptors, Notch/metabolism
مستخلص: The Notch pathway transmits signals between neighboring cells to elicit downstream transcriptional programs. Notch is a major regulator of cell fate specification, proliferation, and apoptosis, such that aberrant signaling leads to a pleiotropy of human diseases, including developmental disorders and cancers. The pathway signals through the transcription factor CSL (RBPJ in mammals), which forms an activation complex with the intracellular domain of the Notch receptor and the coactivator Mastermind. CSL can also function as a transcriptional repressor by forming complexes with one of several different corepressor proteins, such as FHL1 or SHARP in mammals and Hairless in Drosophila. Recently, we identified L3MBTL3 as a bona fide RBPJ-binding corepressor that recruits the repressive lysine demethylase LSD1/KDM1A to Notch target genes. Here, we define the RBPJ-interacting domain of L3MBTL3 and report the 2.06 Å crystal structure of the RBPJ-L3MBTL3-DNA complex. The structure reveals that L3MBTL3 interacts with RBPJ via an unusual binding motif compared to other RBPJ binding partners, which we comprehensively analyze with a series of structure-based mutants. We also show that these disruptive mutations affect RBPJ and L3MBTL3 function in cells, providing further insights into Notch mediated transcriptional regulation.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: T32 ES007250 United States ES NIEHS NIH HHS; R01 CA178974 United States CA NCI NIH HHS
المشرفين على المادة: 0 (DNA-Binding Proteins)
0 (FHL1 protein, human)
EC 1.14.11.- (Histone Demethylases)
0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
0 (Intracellular Signaling Peptides and Proteins)
EC 1.5.- (KDM1A protein, human)
0 (L3MBTL3 protein, human)
0 (LIM Domain Proteins)
0 (Muscle Proteins)
0 (RBPJ protein, human)
0 (Receptors, Notch)
تواريخ الأحداث: Date Created: 20221208 Date Completed: 20230111 Latest Revision: 20230127
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9825171
DOI: 10.1093/nar/gkac1137
PMID: 36477367
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkac1137