LAUSR

Oncogene-induced senescence (OIS) serves as an important barrier to tumor progression in cells that have acquired activating mutations in RAS and other oncogenes. Senescent cells also produce a secretome known as the senescence-associated secretory phenotype (SASP) that includes pro-inflammatory cytokines and chemokines. SASP factors reinforce and propagate the senescence program and identify senescent cells to the immune system for clearance. The OIS program is executed by several transcriptional effectors that include p53, RB, NF-κB and C/EBPβ. In this review, we summarize the critical role of C/EBPβ in regulating OIS and the SASP. Post-translational modifications induced by oncogenic RAS signaling control C/EBPβ activity and dimerization, and these alterations switch C/EBPβ to a pro-senescence form during OIS. In addition, C/EBPβ is regulated by a unique 3'UTR-mediated mechanism that restrains its activity in tumor cells to facilitate senescence bypass and suppression of the SASP.