Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence.
Masashi Narita,Sabrina Nuñez,Sabrina Nuñez,Edith Heard,Masako Narita,Athena W. Lin,Stephen Hearn,David L. Spector,Gregory J. Hannon,Scott W. Lowe +9 more
TLDR
A distinct heterochromatic structure that accumulates in senescent human fibroblasts is described, which is designated senescence-associated heterochROMatic foci (SAHF) and is associated with the stable repression of E2F target genes.About:
This article is published in Cell.The article was published on 2003-06-13 and is currently open access. It has received 2055 citations till now. The article focuses on the topics: Senescence-associated heterochromatin focus & E2F.read more
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A double dealing tale of p63: an oncogene or a tumor suppressor.
TL;DR: It is concluded that p63 may act as either an oncogene or a tumor suppressor gene in different scenarios: TA and ΔN isoforms of p63 gene may initiate tumorigenesis via promoting cell proliferation and survival, but inhibit tumor metastasis and progression.
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Telomerase promoter reprogramming and interaction with general transcription factors in the human mesenchymal stem cell.
TL;DR: It is shown that repression of hTERT expression in hMSCs is due to promoter-specific histone hypoacetylation coupled with low Pol II and TFIIB trafficking and that modifications of the chromatin environment lead to reactivation of telomerase gene expression.
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The Interchromatin Compartment Participates in the Structural and Functional Organization of the Cell Nucleus
Thomas Cremer,Marion Cremer,Barbara Hübner,Asli Silahtaroglu,Michael J. Hendzel,Christian Lanctôt,Hilmar Strickfaden,Christoph Cremer +7 more
TL;DR: The role of the interchromatin compartment (IC) in shaping nuclear landscapes is focused on and it is postulated that it provides routes for imported transcription factors to target sites, for export routes of mRNA as ribonucleoproteins toward NPCs, as well as for the intranuclear passage of regulatory RNAs from sites of transcription to remote functional sites.
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IGFBP-rP1 induces p21 expression through a p53-independent pathway, leading to cellular senescence of MCF-7 breast cancer cells
Shuguang Zuo,Chang Liu,Jianguo Wang,Fuqing Wang,Wanling Xu,Shao Cui,Lei Yuan,Xu-Dong Chen,Wen-Juan Fan,Ming-chen Cui,Guo-Hua Song +10 more
TL;DR: Results from this study suggest that cellular senescence induced by IGFBP-rP1 is mediated at least in part by p21 enhanced expression, which regulated through the p53-independent pathway.
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E2F-1 is a critical modulator of cellular senescence in human cancer
TL;DR: This work shows that E2F1, a transcription factor essential to a cell cycle progress and a main target of tumor suppressor Rb, is a critical barrier for the induction of senescence, and provides insights into the possibility of using E 2F1 as a therapeutic target in the treatment of cancer.
References
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A biomarker that identifies senescent human cells in culture and in aging skin in vivo
Goberdhan P. Dimri,X Lee,G Basile,Meileen Acosta,G Scott,C Roskelley,E E Medrano,Maarten H.K. Linskens,Ivica Rubelj,Olivia M. Pereira-Smith +9 more
TL;DR: It is shown that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture, which provides in situ evidence that senescent cells may exist and accumulate with age in vivo.
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The limited in vitro lifetime of human diploid cell strains
TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
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Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
TL;DR: It is shown that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
Andrew J. Bannister,Philip Zegerman,Janet F. Partridge,Eric A. Miska,Jean O. Thomas,Robin C. Allshire,Tony Kouzarides +6 more
TL;DR: A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.