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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Cell fusion induced by ERVWE1 or measles virus causes cellular senescence.
Anna Chuprin,Hilah Gal,Tal Biron-Shental,Tal Biron-Shental,Anat Biran,Aliza Amiel,Aliza Amiel,Shmuel Rozenblatt,Valery Krizhanovsky +8 more
TL;DR: Fusion-inducedsenescence might be needed for proper syncytiotrophoblast function during embryonic development, and reuse of this senescence program later in life protects against pathological expression of endogenous fusogens and fusogenic viral infections.
Journal ArticleDOI
Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases
Chiara Cencioni,Francesco Spallotta,Fabio Martelli,Sergio Valente,Antonello Mai,Andreas M. Zeiher,Carlo Gaetano +6 more
TL;DR: Here, it is reviewed how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology to help the development of anti-ageing therapies.
Journal ArticleDOI
Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis.
Alyssa L. Kennedy,Jennifer P. Morton,Indrani Manoharan,David M. Nelson,Nigel B. Jamieson,Nigel B. Jamieson,Jeff S. Pawlikowski,Tony McBryan,Brendan Doyle,Colin J. McKay,Karin A. Oien,Greg H. Enders,Rugang Zhang,Owen J. Sansom,Peter D. Adams +14 more
TL;DR: Based on a comparative molecular analysis, it is shown that activated PIK3CA/AKT is a weaker inducer of senescence than is activated RAS, and that this new understanding can be exploited in rational development and targeted application of prosenescence cancer therapies.
Journal ArticleDOI
C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells
Dazhong Zhuang,Sudha Mannava,Sudha Mannava,Vladimir Grachtchouk,Vladimir Grachtchouk,Wenhua Tang,Suresh B. Patil,Joseph A. Wawrzyniak,A. E. Berman,Thomas J. Giordano,Edward V. Prochownik,Maria S. Soengas,Mikhail A. Nikiforov,Mikhail A. Nikiforov +13 more
TL;DR: One of the major functions of C-MYC overexpression in melanoma progression is to continuous suppress BRAFV600E- or NRASQ61R-dependent senescence programs, which agrees with the generally higher rates of activating mutations in BRAF than NRAS gene in human cutaneous melanomas.
Journal ArticleDOI
Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland.
TL;DR: It is concluded that deregulated E2F activity is not sufficient to fully mimic loss of Rb due to the engagement of a senescence response, and the retinoblastoma gene is one of the most frequently mutated genes in human 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.
Journal ArticleDOI
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.