Regulation of the novel senescence pathway by SKP2 E3 ligase

Cellular senescence, a stress response triggered by multiple stimuli, results in a form of irreversible cell cycle arrest that can serve as a critical barrier for cancer development. Various studies have demonstrated the critical role of ARF/p53 pathways in the induction of cellular senescence by activation of oncogenic pathways through overexpression of oncogenes, such as Ras, or by inactivation of tumor suppressor genes, such as PTEN. Recent studies also uncover novel ARF/p53-independent cellular senescence pathways in restricting tumorigenesis. Given that ARF/p53 pathways play an essential role in tumor suppression and are often inactivated in human cancers through defi ciency or mutations of ARF or p53, better understanding of these pathways governing the induction of senescence in human cancer will pave the ways for developing effective pro-senescence therapies. Thus, it’s important to screen current available drugs that stabilize p53 expression for the ability totarget possibility that these Arf-p53 dependent pathways or by developing novel inhibitors to target the Arf- p53 independent pathways.