Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells
| Autor: | Oliver Bischof, Moussa Benhamed, Tao Ye, Anne Dejean, Utz Herbig |
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| Přispěvatelé: | Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from Ligue Nationale Contre le Cancer (Equipe labellisée), Association for International Cancer Research, Agence Nationale de la Recherche, Association pour la Recherche sur le Cancer (ARC), OdysseyRe and the New Jersey Commission on Cancer Research 09-1124-CCR-EO to U.H. O.B. is a CNRS (Centre National de la Recherche Scientifique) fellow, A.D. Institut National de la Santé et de la Recherche Médicale (INSERM)/Institut Pasteur and M.B. was supported by ARC., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cheriet Rauline, Samia |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
MESH: Signal Transduction
[SDV]Life Sciences [q-bio] Endogeny MESH: Base Sequence Retinoblastoma Protein 0302 clinical medicine MESH: Argonaute Proteins Heterochromatin MESH: Reverse Transcriptase Polymerase Chain Reaction MESH: Gene Silencing Promoter Regions Genetic Cellular Senescence Oligonucleotide Array Sequence Analysis MESH: Chromatin Immunoprecipitation 0303 health sciences Effector Reverse Transcriptase Polymerase Chain Reaction Cell biology [SDV] Life Sciences [q-bio] MESH: Heterochromatin MESH: E2F Transcription Factors 030220 oncology & carcinogenesis Argonaute Proteins Protein Binding Signal Transduction Senescence MESH: Cell Nucleus Chromatin Immunoprecipitation MESH: Cell Line Tumor MESH: Mutation Blotting Western Biology Article Cell Line 03 medical and health sciences MESH: Gene Expression Profiling Cell Line Tumor microRNA MESH: Promoter Regions Genetic Gene silencing Humans MESH: Protein Binding MESH: Blotting Western Gene Silencing Psychological repression 030304 developmental biology Cell Nucleus Binding Sites MESH: Humans Base Sequence Gene Expression Profiling MESH: Cellular Senescence Cell Biology MESH: Retinoblastoma Protein eye diseases E2F Transcription Factors MESH: Cell Line Gene expression profiling MicroRNAs MESH: Binding Sites Mutation MESH: Oligonucleotide Array Sequence Analysis Cancer research Chromatin immunoprecipitation MESH: MicroRNAs |
| Zdroj: | Nature Cell Biology Nature Cell Biology, Nature Publishing Group, 2012, 14 (3), pp.266-275. ⟨10.1038/ncb2443⟩ Nature Cell Biology, 2012, 14 (3), pp.266-275. ⟨10.1038/ncb2443⟩ |
| ISSN: | 1465-7392 1476-4679 |
| DOI: | 10.1038/ncb2443⟩ |
| Popis: | International audience; Cellular senescence is a tumour-suppressor mechanism that is triggered by cancer-initiating or promoting events in mammalian cells. The molecular underpinnings for this stable arrest involve transcriptional repression of proliferation-promoting genes regulated by the retinoblastoma (RB1)/E2F repressor complex. Here, we demonstrate that AGO2, RB1 and microRNAs (miRNAs), as exemplified here by let-7, physically and functionally interact to repress RB1/E2F-target genes in senescence, a process that we call senescence-associated transcriptional gene silencing (SA-TGS). Herein, AGO2 acts as the effector protein for let-7-directed implementation of silent-state chromatin modifications at target promoters, and inhibition of the let-7/AGO2 effector complex perturbs the timely execution of senescence. Thus, we identify cellular senescence as the an endogenous signal of miRNA/AGO2-mediated TGS in human cells. Our results suggest that miRNA/AGO2-mediated SA-TGS may contribute to tumour suppression by stably repressing proliferation-promoting genes in premalignant cancer cells. |
| Databáze: | OpenAIRE |
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