regulation of signal transduction by p53 class mediator

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of signal transduction by p53 class mediator. [GOC:TermGenie]

The p53 class mediator, also known as p53-binding protein 1 (53BP1), is a crucial regulator of DNA damage response pathways. It plays a pivotal role in the intricate process of signal transduction, ensuring appropriate cellular responses to DNA damage. Upon DNA damage, p53 undergoes activation and initiates a cascade of events that ultimately lead to cell cycle arrest, DNA repair, or apoptosis. Here's a detailed breakdown of the biological process of signal transduction regulated by p53 class mediator:

1. **DNA damage recognition:** The p53 class mediator, specifically 53BP1, is recruited to sites of DNA damage, often at double-strand breaks, through interactions with the MRN complex (MRE11-RAD50-NBS1).

2. **Chromatin remodeling:** Once at the damaged site, 53BP1 interacts with various histone modifiers, including histone H2AX and the histone methyltransferase SETDB1. This interaction leads to the formation of a repressive chromatin environment at the break, blocking access for DNA repair factors that promote error-prone repair pathways.

3. **Activation of p53 signaling:** 53BP1 further interacts with p53, a crucial transcription factor, and its upstream regulators, such as ATM and ATR kinases. This interaction promotes the activation of p53 through phosphorylation and stabilization, allowing p53 to translocate to the nucleus and initiate its downstream functions.

4. **Cell cycle arrest and DNA repair:** Activated p53 triggers the transcription of target genes involved in cell cycle arrest, such as p21 and 14-3-3 sigma. This pause in the cell cycle provides time for DNA repair mechanisms to function effectively. 53BP1 also promotes homologous recombination, a high-fidelity repair pathway, by interacting with the BRCA1-A complex, a key player in homologous recombination.

5. **Apoptosis induction:** If the DNA damage is too severe or repair mechanisms fail, p53 can trigger the expression of pro-apoptotic genes, such as Bax and Puma. This induction of apoptosis eliminates severely damaged cells, preventing their propagation and potential tumor formation.

In summary, the p53 class mediator, 53BP1, acts as a critical signal transducer in the DNA damage response pathway. By orchestrating chromatin remodeling, promoting p53 activation, and influencing downstream responses like cell cycle arrest, DNA repair, and apoptosis, 53BP1 plays a crucial role in ensuring the integrity of the genome and protecting cells from the detrimental effects of DNA damage.'
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Proteins (51)

Compounds (543)