PML is induced by oncogenicrasand promotes premature senescence

• DOI: 10.1101/gad.14.16.2015
• Publication Date: 2021-11-15T03:35:00Z
• Authors: Gerardo Ferbeyre; Elisa de Stanchina; Emmanuelle Querido; Nicole Baptiste; Carol Prives; Scott W. Lowe
• Keywords: Promyelocytic leukemia protein; Senescence; Retinoblastoma protein; Phosphoserine

Oncogenic ras provokes a senescent-like arrest in human diploid fibroblasts involving the Rb and p53 tumor suppressor pathways. To further characterize this response, we compared gene expression patterns between -arrested quiescent IMR90 fibroblasts. One of genes up-regulated during -induced was promyelocytic leukemia (PML) protein, potential that encodes component nuclear structures known as oncogenic domains (PODs). PML levels increased both replicative senescence, leading to dramatic increase size number PODs. Forced sufficient promote premature senescence. Like ras, p16, hypophosphorylated Rb, phosphoserine-15 p53, transcriptional targets. The fraction colocalized with markedly arrest, alone forced E1A abolished prevented induction phosphorylation response . These results imply acts senescence provide new insights into regulation activity.