Transcriptional regulation by p53: one protein, many possibilities

Abstract

The p53 tumor suppressor protein is a DNA sequence-specific transcriptional regulator that, in response to various forms of cellular stress, controls the expression of numerous genes involved in cellular outcomes including among others, cell cycle arrest and cell death. Two key features of the p53 protein are required for its transcriptional activities: its ability to recognize and bind specific DNA sequences and to recruit both general and specialized transcriptional co-regulators. In fact, multiple interactions with co-activators and corepressors as well as with the components of the general transcriptional machinery allow p53 to either promote or inhibit transcription of different target genes. This review focuses on some of the salient features of the interactions of p53 with DNA and with factors that regulate transcription. We discuss as well the complexities of the functional domains of p53 with respect to these interactions.

Apoptosis-mediated testicular alteration in Japanese quail (Coturnix coturnix japonica) in response to temporal phase relation of serotonergic and dopaminergic oscillations

“…p53-mediated apoptosis can occur by way of trans-activation of Bax or trans-suppression of Bcl-2. p53 activation/overexpression stimulates pro-apoptotic Bax expression, which warps Bcl-2 and reduces the Bcl-2/Bax ratio (Laptenko and Prives, 2006). However, p53 possesses a dual mechanism that alternates between transactivation and trans-suppression.…”

p53 promotes cellular survival in a context-dependent manner by directly inducing the expression of haeme-oxygenase-1

“…However, if the damage is limited, the cell-cycle is halted and the DNA-repair pathways are activated to correct the defects (Helton and Chen, 2007). Years of research have indicated that either of these mechanisms can predominate, based on cooperation with various cellular cofactors, depending on the cellular context and extent of damage (Laptenko and Prives, 2006;Brooks and Gu, 2010).…”

Are interactions with p63 and p73 involved in mutant p53 gain of oncogenic function?

“…Under a variety of stress conditions, wild-type p53 protein quickly accumulates in the nucleus and can then transcriptionally regulate a number of downstream genes that control cell cycle arrest or apoptosis (reviewed by Vogelstein et al, 2000;Laptenko and Prives, 2006). In addition, wild-type p53 can contribute to apoptosis through transcriptionindependent pathway(s) in the cytosol (reviewed by Chipuk and Green, 2006).…”