Fig. 2.

Nucleolus under stress. The nucleolus plays a central role during the cellular response to stress. Under normal conditions, p53 is kept at very low level by proteasomal mediated degradation through ubiquitination by MDM2. Following activation of stress responses, oncogene activation or DNA damage, the p14ARF tumor suppressor normally located in the nucleolus associates with HDM2 and sequesters it within the nucleolus. This segregation prevents the ubiquitination of p53 mediated by HDM2 resulting in increased levels of cellular p53 resulting in cell cycle arrest and apoptosis