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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
Oncogenic ras can transform most immortal rodent cells to a tumorigenic state. However, transformation of primary cells by ras requires either a cooperating oncogene or the inactivation of tumorExpand
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The Hallmarks of Aging
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for majorExpand
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Cellular senescence: from physiology to pathology
Recent discoveries are redefining our view of cellular senescence as a trigger of tissue remodelling that acts during normal embryonic development and upon tissue damage. To achieve this, senescentExpand
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Role of the INK4a Locus in Tumor Suppression and Cell Mortality
The cell cycle inhibitor p16INK4a is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer. Tumor-associated alterations in the INK4a locus may also affectExpand
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Cellular Senescence in Cancer and Aging
Cellular senescence, a state of irreversible growth arrest, can be triggered by multiple mechanisms including telomere shortening, the epigenetic derepression of the INK4a/ARF locus, and DNA damage.Expand
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Tumour biology: Senescence in premalignant tumours
Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have beenExpand
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Sirt1 protects against high-fat diet-induced metabolic damage
The identification of new pharmacological approaches to effectively prevent, treat, and cure the metabolic syndrome is of crucial importance. Excessive exposure to dietary lipids causes inflammatoryExpand
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The Ink4/Arf locus is a barrier for iPS cell reprogramming
The mechanisms involved in the reprogramming of differentiated cells into induced pluripotent stem (iPS) cells by the three transcription factors Oct4 (also known as Pou5f1), Klf4 and Sox2 remainExpand
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A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity
The reprogramming of differentiated cells to pluripotent cells (induced pluripotent stem (iPS) cells) is known to be an inefficient process. We recently reported that cells with short telomeresExpand
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Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling.
Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part, by constitutively transmitting mitogenic signals through the mitogen-activated protein kinase (MAPK) cascade. InExpand
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