Early growth response 2 (EGR2) is a novel regulator of the senescence programme

Senescence, a state of stable growth arrest, plays an important role in ageing and age-related diseases vivo. Although the INK4/ARF locus is known to be essential for senescence programmes, key regulators driving p16 ARF transcription remain largely underexplored. Using siRNA screening modulators p16/pRB ARF/p53/p21 pathways deeply senescent human mammary epithelial cells (DS HMECs) fibroblasts HMFs), we identified EGR2 as novel regulator senescence. expression up-regulated during senescence, its ablation by DS HMECs HMFs transiently reverses phenotype. We demonstrate that activates promoters directly binds both promoters. Loss down-regulates levels increases pool p16− p21− ‘reversed’ population. Moreover, overexpression sufficient induce Our data suggest direct transcriptional activator marker