Mechanisms of p53 activation and regulation of downstream targets (Riley et al. 2002).
p53 is an important tumor suppressor protein that plays a critical role in genomic stability and cell regulation in humans. p53 is activated in response to cell stress signals, such as those emitted from a double-strand DNA break. Once activated, p53 is able to bind specific response elements in p53-regulated genes (Inga et al. 2002). p53 binds to these response elements in the promoter sequence upstream of the transcription start site and recruits cofactors that interact with p53 to either promote or inhibit transcription of the gene of interest (Beckerman et al. 2010).
p53 regulates several genes involved in a wide variety of cell processes, including cell-cycle arrest, repair, and apoptosis (Riley et al. 2008). It can halt cell growth by stopping the cell cycle when DNA damage is detected. If the damage is repairable, it will activate proteins involved in DNA repair. If the damage is found to be irreparable, p53 will then initiate apoptosis to terminate the cell.
p53-mediated apoptosis.
References[]
- Rachel Beckermen and Carol Prives. (2010). Transcriptional Regulation by p53 . Cold Spring Harbor Perspectives in Biology, 2(8): a000935.
- Alberto Inga, Francesca Storici, Thomas A Darden, and Michael A Resnick. (2002). Differential transactivation by the p53 transcription factor is highly dependent on p53 level and promoter target sequence. Molecular and Cellular Biology, 22(24): 8612–8625.
- Todd Riley, Eduardo Sontag, Patricia Chen, and Arnold Levine. (2008). Transcriptional control of p53-regulated genes . Nature Reviews Molecular Cell Biology, 9(5): 402–412.
Pages[]
- Keri: p53: Introduction
- Keri: p53: Biological function
- Keri: p53: Biosynthesis
- Keri: p53: Gene sequence
- Keri: p53: Amino acid sequence and composition
- Keri: p53: Secondary and tertiary structure
- Keri: p53: Domains and structural motifs
- Keri: p53: Interactions with macromolecules and small molecules
- Keri: p53: Molecular biodiversity and evolution
- Keri: p53: Literature overview
- Keri: p53: Useful online resources