Effects of p21Waf1/Cip1/Sdi1 on cellular gene expression: implications for carcinogenesis, senescence, and age-related diseases.
Bey-Dih Chang,Keiko Watanabe,Eugenia V. Broude,Jing Fang,Jason C. Poole,Tatiana V. Kalinichenko,Igor B. Roninson +6 more
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The results suggest that the effects of p21 induction on gene expression in senescent cells may contribute to the pathogenesis of cancer and age-related diseases.Abstract:
Induction of cyclin-dependent kinase inhibitor p21(Waf1/Cip1/Sdi1) triggers cell growth arrest associated with senescence and damage response. Overexpression of p21 from an inducible promoter in a human cell line induces growth arrest and phenotypic features of senescence. cDNA array hybridization showed that p21 expression selectively inhibits a set of genes involved in mitosis, DNA replication, segregation, and repair. The kinetics of inhibition of these genes on p21 induction parallels the onset of growth arrest, and their reexpression on release from p21 precedes the reentry of cells into cell cycle, indicating that inhibition of cell-cycle progression genes is a mechanism of p21-induced growth arrest. p21 also up-regulates multiple genes that have been associated with senescence or implicated in age-related diseases, including atherosclerosis, Alzheimer's disease, amyloidosis, and arthritis. Most of the tested p21-induced genes were not activated in cells that had been growth arrested by serum starvation, but some genes were induced in both forms of growth arrest. Several p21-induced genes encode secreted proteins with paracrine effects on cell growth and apoptosis. In agreement with the overexpression of such proteins, conditioned media from p21-induced cells were found to have antiapoptotic and mitogenic activity. These results suggest that the effects of p21 induction on gene expression in senescent cells may contribute to the pathogenesis of cancer and age-related diseases.read more
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p21 in cancer: intricate networks and multiple activities
Tarek Abbas,Anindya Dutta +1 more
TL;DR: This Review focuses on recent advances in the understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.
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Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors
Judith Campisi,Judith Campisi +1 more
TL;DR: The senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate.
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The role of the cyclin-dependent kinase inhibitor p21 in apoptosis.
Andrei L. Gartel,Angela L. Tyner +1 more
TL;DR: The role of p21 in regulating cell death and the potential relevance of its expression in cancer are discussed and this may counteract its tumor-suppressive functions as a growth inhibitor.
Journal ArticleDOI
Senescence is a developmental mechanism that contributes to embryonic growth and patterning.
Mekayla Storer,Alba Mas,Alexandre Robert-Moreno,Matteo Pecoraro,M. Carmen Ortells,Valeria Di Giacomo,Reut Yosef,Noam Pilpel,Valery Krizhanovsky,James Sharpe,William M. Keyes +10 more
TL;DR: It is proposed that senescence is a normal programmed mechanism that plays instructive roles in development, and that OIS is an evolutionarily adapted reactivation of a developmental process.
Journal ArticleDOI
Cellular senescence as a tumor-suppressor mechanism.
TL;DR: Findings have revealed the complexities of the senescence phenotype and unexpected possible consequences for the organism.
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