Selected targets of p53
Selected targets of p53 Tumor protein p53 ( p53 ) is active as a tetramer consisting of four identicalchains of 393 amino acid residues. The N-terminal region contains an intrinsicallydisordered trans-activation domain (TAD) and a proline-rich region. The central, foldedDNA-binding core domain, is responsible for sequence-specific DNA binding. At itsC-terminus, p53 contains the so-called regulatory domain. This natively unfoldedregion is rich in basic amino acids (mainly lysines) and binds DNA nonspecifically . p53 is normally activated by cellular stress and mediates thegrowth-suppressive response that involves cell cycle arrest and apoptosis . In the case of cell cycle arrest, Cyclin-dependent kinase inhibitor 1A (p21 ) appears sufficient to block cell cycle progression out of G1 until DNArepair has occurred, or the cellular stress has been alleviated , . The p53 -dependent apoptotic response is complex and involves transcriptionalactivation of multiple pro-apoptotic target genes . There are, forexample, different caspases , Cathepsin D , Bcl-2family members (B-cell CLL/lymphoma 2 ( Bcl-2 ) and BCL2-associated X protein (Bax ))  and BCL2/adenovirus E1B 19kDa interacting protein 3-like (NIX ) . The p53 pathway, either directly or indirectly, is targeted for inactivationin most human cancers. The latter highlights the protein's critical function as a tumorsuppressor gene . This pathway is realized mostly via regulation oftranscription of developmental signaling genes. for example of tumor suppressorsHypermethylated in cancer 1 and 2 ( HIC1/2 ) , Brain-specificangiogenesis inhibitor 1 ( BAI1 ) , PTK6 protein tyrosine kinase 6( BRK ) , Adenomatous polyposis coli ( APC protein ) . In addition, p53 participates in regulation of transport ,cytoskeletal signaling , ECM and adhesion , proteintraffic  and others processes. Possibly, most of these processes takepart in development of the basic p53 -denendent response (apoptosis, cell cyclearrest, tumor suppression).