Nuclear protein p53 plays an essential role in the regulation of cell cycle, specifically in the transition from G0 to G1. p53 is a DNA-binding protein containing DNA-binding, oligomerization and transcription activation domains. It is postulated to bind as a tetramer to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer, which includes cancer of colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. p53 maps to the 17p13.1 region of the human chromosome.
Consistent with its role as a tumor suppressor gene in a wide variety of tissue types, p53 performs several different critical functions in regulating cellular growth, replication, and death. p53 positively regulates transcription by binding to specific DNA consensus sequences. These sequences are associated with several known genes including the human ribosomal gene cluster, muscle creatine kinase gene, WAF-1/CIPI/p21, and cyclin G. This sequence-specific transcriptional activation is associated with the induction of growth suppression. p53 also negatively regulates transcription of genes which have TATA box initiated promoters, likely by binding to protein components of the basal transcription machinery. Possibly through the general mechanism of transcriptional regulation, p53 affects cell behavior via several specific pathways.
Wild-type p53 suppresses cell proliferation by blocking the transition from G1 to S-phase. This may occur through p53 mediated induction of a universal inhibitor of cyclin-dependent kinases, WAF-1 or CIPI. Increased expression of WAF 1/CIPI/p21 serves to inhibit phosphorylation of Rb protein by cdk complexes, resulting in failure to progress from G1 to S phase.
This p53 antibody recognizes a 53kDa protein, which is identified as p53 suppressor gene product. The antibody reacts with the mutant as well as the wild form of p53 under denaturing and non-denaturing conditions. The epitope maps within the N-terminus (aa 20-25) of p53 oncoprotein.
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