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Module 11: Figure senescence

Mechanisms of cell senescence.

Normal cells can transform into a non-proliferating senescent state through two main mechanisms. Loss of telomeres results in replicative senescence. A variety of cellular stresses, including the activation of oncogenes, results in stress-induced senescence. The latter is induced by two main pathways. Oncogenes such as Ras and Myc can activate tumour suppressors, such as p16 and alternative reading frame (ARF), that act through E2F/retinoblastoma protein (Rb) and p53 respectively to divert cells into stress-induced senescence. These senescence pathways are avoided or switched off during the development of cancer cells. The expression of telomerase avoids the replicative senescence pathway, whereas the inactivation of the tumour suppressors such as Rb, p16 or p53 prevents the emerging cell from being diverted into stress-induced senescence.