p53 is a tumor suppressor that has a central role in regulating cell cycle arrest, DNA repair, and apoptosis. p53 is widely studied for its role in cancer and is mutated or altered in more than half of all cancers (1). This widespread role in tumorigenesis has made p53 one of the most highly studied proteins and a target for anti-cancer therapeutics. Normally, p53 allows cells to sense and respond to cellular stress such as DNA damage or hypoxia (2). In response to these signals, p53 is activated through post-translational modification and protein stabilization. This allows p53 to bind DNA and regulate the expression of various genes (2). p53 can control diverse transcriptional programs to regulate senescence and cell death programs as well as cellular metabolism (2). p53 integrates a variety of signals and allows cells to respond in a manner that is highly dependent on cellular context (2). In addition to its role as a transcription factor, p53 functions in the cytoplasm to regulate the activity of apoptotic pathway proteins such as BAX, BAK, and BCL-2 (2). Although the mechanisms are still unclear, p53 is thought to regulate these apoptotic proteins through direct interaction (2). p53 has important roles in normal physiology and pathological conditions. Further investigations will help to elucidate the complex mechanisms of p53 regulation (2).
Given p53's overexpression in a majority of cancers, p53 antibodies have been widely used as prognostic indicators for many years. For example, a monoclonal p53 antibody, thought to recognize only an epitope on the mutated p53 protein, has been used to assess prognosis and survival rates for colorectal cancer (3). Through ELISA and flow cytometry this study showed strong correlation between mutant p53 levels and survival rates (3). Investigation of p53 activation has revealed protein stability in an important aspect of p53 activity. In one study western blotting with p53 antibody was used to measure the half-life of p53 protein (4). This study revealed proteins involved in oxidative stress are able to inhibit p53 degradation (4). Western blotting or immunofluorescence with p53 antibodies is also widely used to monitor induction of DNA damage pathways (5). A recent example from the MD Anderson Cancer Center followed p53 induction following UV-irradiation to assess DNA repair in a mouse model of skin carcinogenesis (5). The applications of p53 antibodies range from assessing protein levels and post-translational modifications to examining interactions with binding partners or occupancy at a gene locus. These techniques are essential for understanding p53's complex role in regulating cell behavior.
Novus Biologicals offers p53 reagents for your research needs including:
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