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
Citations
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The mTORC1 Inhibitor Everolimus Prevents and Treats Eμ-Myc Lymphoma by Restoring Oncogene-Induced Senescence
Meaghan Wall,Gretchen Poortinga,Kym Stanley,Ralph K. Lindemann,Michael Bots,Christopher J. Chan,Megan J. Bywater,Kathryn M. Kinross,Megan Victoria Astle,Kelly Waldeck,Katherine M. Hannan,Jake Shortt,Mark J. Smyth,Scott W. Lowe,Ross D. Hannan,Richard B. Pearson,Ricky W. Johnstone,Grant A. McArthur +17 more
TL;DR: Novel insights are provided into the requirements for MYC-induced oncogenesis by showing that mTORC1 activity is necessary to bypass senescence during transformation of B lymphocytes, which identifies a previously uncharacterized mechanism responsible for significant anticancer activity of rapamycin analogues.
Journal ArticleDOI
Differential expression of SUMO-specific protease 7 variants regulates epithelial–mesenchymal transition
Tasneem Bawa-Khalfe,Long Sheng Lu,Yong Zuo,Chao Huang,Ruhee Dere,Feng-Ming Lin,Edward T.H. Yeh,Edward T.H. Yeh +7 more
TL;DR: It is shown that SENP7L induction promotes gene expression profiles that favor aberrant proliferation and initiate epithelial–mesenchymal transition (EMT) and stable knockdown of elevated SENP 7L levels lessens the dissemination of highly metastatic BCa cells to the lungs from primary implantation sites in in vivo studies.
Journal ArticleDOI
Activation of Bmp2-Smad1 Signal and Its Regulation by Coordinated Alteration of H3K27 Trimethylation in Ras-Induced Senescence
Atsushi Kaneda,Takanori Fujita,Motonobu Anai,Shogo Yamamoto,Genta Nagae,Masato Morikawa,Shingo Tsuji,Masanobu Oshima,Kohei Miyazono,Hiroyuki Aburatani +9 more
TL;DR: It was revealed through genome-wide analyses in this study that Bmp2-Smad1 signal and its regulation by harmonized epigenomic alteration play an important role in Ras-induced senescence.
Journal ArticleDOI
Cellular Senescence and Lung Function during Aging. Yin and Yang
TL;DR: There are now transgenes and prototype small molecules that can clear senescent cells, at least in mouse models, and thus improve health span and median life span and the next challenge will be to develop interventions and supplements that can abrogate the deleterious effects of senescence while preserving their beneficial effects.
Journal ArticleDOI
Polymer Modeling Predicts Chromosome Reorganization in Senescence.
Michael F. Chiang,Davide Michieletto,Davide Michieletto,Davide Michieletto,Chris A. Brackley,Nattaphong Rattanavirotkul,Hisham Mohammed,Davide Marenduzzo,Tamir Chandra +8 more
TL;DR: This model explains the conventional organization of heterochromatin and euchromatin in growing cells and the pathological organization found in oncogene-induced senescence and progeria and suggests that the senescent phenotype should be metastable even if lamina-mediated interactions were reinstated.
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.