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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Tethering by lamin A stabilizes and targets the ING1 tumour suppressor.
Xijing Han,Xiaolan Feng,Jerome B. Rattner,Heather SmithH. Smith,Pinaki Bose,Keiko Suzuki,Mohamed A. Soliman,Mohamed A. Soliman,Michelle S. Scott,Brian Burke,Karl Riabowol +10 more
TL;DR: Data show that targeting of ING1 to the nucleus by lamin A maintains InG1 levels and biological function, indicating that known roles for ING proteins in regulating apoptosis and chromatin structure indicate that loss of lamination A–ING interaction may be an effector ofLamin A loss, contributing to the HGPS phenotype.
Journal ArticleDOI
Senescence and immortality in hepatocellular carcinoma
Mehmet Ozturk,Ayca Arslan-Ergul,Sevgi Bagislar,Sevgi Bagislar,Serif Senturk,Haluk Yuzugullu,Haluk Yuzugullu +6 more
TL;DR: Hepatocellular carcinoma (HCC) cells display inactivating mutations of p53 and epigenetic silencing of p16(INK4a), and they re-express telomerase reverse transcriptase required for telomere maintenance, likely to contribute significantly to HCC development.
Journal ArticleDOI
Reducing Senescent Cell Burden in Aging and Disease.
TL;DR: It is hypothesize that these pharmacologic interventions may have transformative effects on geriatric medicine and target engagement of senolytic agents that clear senescent cells.
Journal ArticleDOI
Epigenetic regulation of cancer growth by histone demethylases
TL;DR: The observation that overexpression, amplification or mutations of several histone demethylases have been found in many types of tumors, raise the possibility of using these enzymes as diagnostic tools as well as pave a way for the discovery of novel therapeutic targets and treatment modalities.
Journal ArticleDOI
Emerging roles of RB family: New defense mechanisms against tumor progression
Paola Indovina,Eleonora Marcelli,Nadia Casini,Valeria Rizzo,Antonio Giordano,Antonio Giordano +5 more
TL;DR: Elucidating the intricate RB protein network in regulating cell fate might provide the knowledge necessary to explain their potent tumor suppressor activity and to design novel therapeutic strategies.
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.
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.