Early growth response 2 (EGR2) is a novel regulator of the senescence program
Early growth response 2 (EGR2) is a novel regulator of the senescence program
Summary Senescence, a state of stable growth arrest, plays an important role in ageing and age-related diseases in vivo. Although the INK4/ARF locus is known to be essential for senescence programs, the key regulators driving p16 and ARF transcription remain largely underexplored. Using siRNA screening for modulators of the p16/pRB and ARF/p53/p21 pathways in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs), we identified EGR2 as a novel regulator of senescence. EGR2 expression is up-regulated during senescence and its ablation by siRNA in DS HMECs and HMFs transiently reverses the senescent phenotype. We demonstrate that EGR2 activates the ARF and p16 promoters and directly binds to the ARF promoter. Loss of EGR2 downregulates p16 levels and increases the pool of p16- p21- ‘reversed’ cells in the population. Moreover, EGR2 overexpression is sufficient to induce senescence. Our data suggest that EGR2 is a regulator of the p16/pRB and direct transcriptional activator of the ARF/p53/p21 pathways in senescence and a novel marker of senescence.
Philpott Michael P、Tyler Eleanor J.、del Arroyo Ana Gutierrez、Koh Jim、Lowe Robert、Bishop Cleo L.、Wallis Ryan、Garbe James C.、Hughes Bethany、Stampfer Martha R.
Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and DentistryBlizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and DentistryTranslational Medicine & Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of LondonDivision of General Surgery, Department of Surgery, UCSFBlizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and DentistryBlizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and DentistryBlizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and DentistryBiological Systems and Engineering Division, Lawrence Berkeley National LaboratoryBlizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and DentistryBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory
基础医学分子生物学细胞生物学
Philpott Michael P,Tyler Eleanor J.,del Arroyo Ana Gutierrez,Koh Jim,Lowe Robert,Bishop Cleo L.,Wallis Ryan,Garbe James C.,Hughes Bethany,Stampfer Martha R..Early growth response 2 (EGR2) is a novel regulator of the senescence program[EB/OL].(2025-03-28)[2025-05-05].https://www.biorxiv.org/content/10.1101/2020.09.30.321190.点此复制
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