The cellular response to p53: the decision between life and death

Abstract

The p53 tumor suppressor protein plays a crucial role in regulating cell growth following exposure to various stress stimuli. p53 induces either growth arrest, which prevents the replication of damaged DNA, or programmed cell death (apoptosis), which is important for eliminating defective cells. Whether the cell enters growth arrest or undergoes apoptosis, depends on the ®nal integration of incoming signals with antagonistic eects on cell growth. Many factors aect the cellular response to activated p53. These include the cell type, the oncogenic status of the cell with emphasis on the Rb/E2F balance, the extracellular growth and survival stimuli, the intensity of the stress signals, the level of p53 expression and the interaction of p53 with speci®c proteins. p53 is regulated both at the levels of protein stability and biochemical activities. This complex regulation is mediated by a range of viral and cellular proteins. This review discusses this intriguing complexity which aects the cell response to p53 activation.

Cellular response to oxidative stress: Signaling for suicide and survival*

“…The tumor suppressor protein p53 is a universal sensor of genotoxic stress and, as a transcription factor, plays a critical role in regulating expression of genes involved in mediating growth arrest and/or cell death in response to such conditions (Burns and El Deiry, 1999;Sionov and Haupt, 1999). ROS appear to be involved at multiple levels in the p53 signaling.…”

“…This is a complex process involving multiple phosphorylation and acetylation events (Sionov and Haupt, 1999;Colman et al, 2000). ROS contribute to p53 activation in many ways.…”

Bcl-2 blocks cisplatin-induced apoptosis by suppression of ERK-mediated p53 accumulation in B104 cells

“…Neurological complications of cisplatin treatment are P53 is a major mediator in DNA damage-induced common and potentially serious. Ototoxicity, peripheral apoptosis [39]. Involvement of p53 in cisplatin-induced neuropathy, cranial neuropathy, and encephalopathy have apoptosis has been demonstrated in several cell types been known as clinical pictures of neurotoxicity [16,21].…”

Resistance of colon cancer cells to long‐term 5‐fluorouracil exposure is correlated to the relative level of Bcl‐2 and Bcl‐XL in addition to Bax and p53 status

“…Among genes of the apoptotic pathway, the p53 tumor suppressor gene is involved in G1 growth arrest by inducing the cyclin dependent kinase inhibitor p21/WAF1 and also in apoptosis through transactivation of the pro-apoptotic bax gene in response to DNA-damage. 5,6 The p53 gene, which is inactivated in a majority of human cancers, 7 has been proposed as an accurate indicator of response of colon cancer to 5-FU. Many studies have correlated p53 status with prognosis and therapy response of tumors.…”