The p53 protein contains several important domains, including transcription activation, DNA-binding, and oligomerization domains . These domains enable p53 to regulate the expression of a large number of genes involved in critical cellular processes such as cell cycle arrest, DNA repair, senescence, and apoptosis . The protein is expressed at low levels in normal cells but is upregulated in response to cellular stress, such as DNA damage, hypoxia, and spindle damage .
Activation of p53 begins through various mechanisms, including phosphorylation by ATM, ATR, Chk1, and MAPKs . One of the key regulators of p53 is MDM2, a ubiquitin ligase that binds to p53 and targets it for proteasomal degradation . Phosphorylation, along with other modifications such as methylation and acetylation, can prevent MDM2-p53 interactions, leading to an increase in stable p53 tetramers in the cytoplasm . These modifications enhance p53’s ability to bind to gene-specific response elements and regulate the expression of target genes .
The p53 protein is a critical component of the cellular response to stress and plays a principal role in tumor suppression . It regulates over 100 genes that control key tumor-suppressing functions, including cell cycle arrest, DNA repair, senescence, and apoptosis . Inactivation of p53 is a common feature in many human cancers, facilitating tumor progression . The high percentage of amino acid sequence identity between p53 proteins in different species underscores its crucial importance in cellular life and tumor suppression .
Recombinant human p53 protein is often produced using various expression systems, such as E. coli, to study its structure and function in detail . The recombinant protein is typically expressed with tags, such as GST, to facilitate purification and characterization . It is supplied in specific buffer formulations to maintain its stability and activity during storage and handling .