Fig. 4.

p53 dependent and independent tumor suppressive functions of ARF. ARF plays a key role in cellular senescence and tumorigenesis through activation of the p53 pathway. ARF binds and sequesters MDM2 in the nucleolus, leading to the activation of p53 in the nucleoplasm. p53 transcribes numerous target genes and activates cellular senescence or apoptosis. ARF also functions in a p53-independent manner through interaction with numerous target proteins. ARF regulates sumoylation, transcription activities, or protein turnover of target proteins, which lead to tumor suppression and senescence.