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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Heart estrogen receptor alpha: Distinct membrane and nuclear distribution patterns and regulation by estrogen
TL;DR: The results indicate that the levels of the cardiac ERalpha isoforms are downregulated by estrogen and are differentially distributed: the full-length ERalpha is mainly compartmentalized in the cytosol and nucleus, while the 45 kDa isoform is mainly present in membrane structures.
Journal ArticleDOI
Mitotic Stress Is an Integral Part of the Oncogene-Induced Senescence Program that Promotes Multinucleation and Cell Cycle Arrest
Dina Dikovskaya,John J. Cole,Susan M. Mason,Colin Nixon,Saadia A. Karim,Lynn McGarry,William Clark,Rachael N. Hewitt,Morgan A. Sammons,Jiajun Zhu,Dimitris Athineos,Joshua D.G. Leach,Francesco Marchesi,John van Tuyn,Stephen W.G. Tait,Claire Brock,Jennifer P. Morton,Hong Wu,Shelley L. Berger,Karen Blyth,Peter D. Adams +20 more
TL;DR: It is shown that multinucleate OIS cells originate mostly from failed mitosis, and activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multin nucleate senescent cells.
Journal ArticleDOI
MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output
Lihong Chen,Zhenyu Li,Aleksandra Zwolinska,Matthew A. Smith,Brittany Cross,John M. Koomen,Zhi-Min Yuan,Thomas Jenuwein,Jean-Christophe Marine,Kenneth L. Wright,Jiandong Chen +10 more
TL;DR: The results suggest that MDM2‐dependent recruitment of methyltransferases is a novel mechanism of p53 regulation through methylation of both p53 itself and histone H3 at target promoters.
Journal ArticleDOI
Cyclin D1 Activity Regulates Autophagy and Senescence in the Mammary Epithelium
Nelson E. Brown,Rinath Jeselsohn,Teeru Bihani,Miaofen G. Hu,Parthena Foltopoulou,Charlotte Kuperwasser,Philip W. Hinds +6 more
TL;DR: It is reported that mouse cyclin D1(KE/KE) MECs upregulate an autophagy-like process but fail to implement ErbB2-induced senescence in vivo, and a previously unrecognized function of cyclIn D1 in suppressing Autophagy in the mammary epithelium is suggested.
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Senolytics and Senomorphics: natural and synthetic therapeutics in the treatment of aging and chronic diseases.
TL;DR: In this paper, the authors present the already identified senolytics and senomorphics focusing on their redox-sensitive properties and suggest the design of future senotherapeutics to target specific redoxregulated signaling pathways implicated either in the regulation of SASP or in the elimination of SC.
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.