Τίτλος:
RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1), modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor κB (NF-κB) dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-κB target genes to augment their transcription. Concordantly, RNF20+/- mice are predisposed to acute and chronic colonic inflammation and inflammation-associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs) that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings. © 2016 The Authors.
Συγγραφείς:
Tarcic, O.
Pateras, I.S.
Cooks, T.
Shema, E.
Kanterman, J.
Ashkenazi, H.
Boocholez, H.
Hubert, A.
Rotkopf, R.
Baniyash, M.
Pikarsky, E.
Gorgoulis, V.G.
Oren, M.
Περιοδικό:
Cell Reports Medicine
Λέξεις-κλειδιά:
histone H2B; protein RNF20; transcription factor RelA; tumor necrosis factor alpha; ubiquitin protein ligase E3; unclassified drug; chromatin; histone; immunoglobulin enhancer binding protein; RNF20 protein, human; ubiquitin protein ligase, animal cell; animal experiment; animal tissue; Article; binding affinity; cell activity; colorectal cancer; controlled study; cytokine response; disease association; disease predisposition; disease severity; DNA damage; down regulation; exon; gene; gene targeting; heterozygosity; human; human cell; IL6 gene; IL8 gene; immunocompetent cell; innate immunity; mouse; nonhuman; priority journal; protein binding; protein function; RNF20 gene; T lymphocyte; ubiquitination; ulcerative colitis; animal; bone marrow cell; chemistry; chromatin; colon; Colorectal Neoplasms; complication; gene expression regulation; genetic transcription; genetics; immunology; inflammation; male; pathology; signal transduction; transgenic mouse; ubiquitination; ulcerative colitis, Animals; Chromatin; Colitis, Ulcerative; Colon; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Histones; Humans; Inflammation; Male; Mice; Mice, Transgenic; Myeloid Cells; NF-kappa B; Signal Transduction; T-Lymphocytes; Transcription, Genetic; Ubiquitin-Protein Ligases; Ubiquitination
DOI:
10.1016/j.celrep.2016.01.020
