Role of p53 family members in apoptosis

Abstract

p53-mediated apoptosis involves multiple mechanisms. A number of p53-regulated apoptosis-related genes have been identified. Some of these genes encode proteins that are important in controlling the integrity of mitochondria while the others code for membrane death receptors. p53 may also induce apoptosis by interfering with the growth factor-mediated survival signals. Although the transactivation-deficient p53 can induce apoptosis, evidence suggests that both the transcription-dependent and independent functions are needed for full apoptotic activity. p73 and p63 are two other members of the p53 family that show homology to p53 in their respective transactivation, DNA-binding and oligomerization domains. Both p73 and p63 transactivate p53-regulated promoters and induce apoptosis. Evidence suggests that both p73 and p63 may mediate apoptosis via some of the same mechanisms that are utilized by p53. However, both p73 and p63 exhibit features that are different from those of p53. Hence, both p73 and p63 are predicted to mediate apoptosis via mechanisms that are completely distinct from those engaged by p53. J. Cell. Physiol. 182:171-181, 2000. Published 2000 Wiley-Liss, Inc.

Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS

“…Typically, p53 is activated when DNA damage occurs or the cell is stressed. It translocates to the nucleus, where it can induce proapoptotic gene expression, such as Bax, on the mitochondrial membrane, activate the effector caspase-3 and accelerate cell death (Levine, 1997;Sheikh and Fornace, 2000). Our results showed that the expression level of Bax progressively increased when the fish was treated with PFOS (Fig.…”

Neutral Sphingomyelinase-3 Is a DNA Damage and Nongenotoxic Stress-Regulated Gene That Is Deregulated in Human Malignancies

“…The tumor suppressor p53 is a major regulator of the cellular response to genotoxic stress (47)(48)(49). One way in which p53 modulates the cellular stress response is by functioning as a transcription factor to regulate the expression of genes important to cell growth arrest and apoptosis, such as p21 WAF1 , PUMA, DR5, and BAX.…”

Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation

“…[3][4][5] PUMA encodes a BH3 only domain proapoptotic protein that localizes to mitochondria and interacts with antiapoptotic Bcl-2 and Bcl-X L (1)(2)(3). It is now well established that the tumor suppressor p53 predominantly functions as a transcription factor and mediates its effects by inducing growth arrest and/or apoptosis (reviewed in Sheikh and Fornace Jr, 6 Vousden and Lu, 7 and Hofseth et al 8 ). p53 mediates its apoptotic effects by transcriptionally activating the expression of proapoptotic genes, some of which include Bax, NOXA, PUMA and DR5, whose products modulate the intrinsic and extrinsic pathways of apoptosis (reviewed in Hofseth et al 8 ).…”