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IMGENEX has now p73 phosphospecific antibody
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Author: Stephen Jones The p53 family member, p73, also known as tumor protein 73 (TP73) has been recently identified as a structural and functional homolog of the tumor suppressor protein p53. In accordance with its structural similarity, p73 functions in a manner analogous to p53 by inducing tumor cell apoptosis and participating in the cell cycle checkpoint control through transactivating an overlapping set of p53/p73-target genes. Under these conditions p73 is tyrosine-phosphorylated by c-Abl, a prerequisite modification for p73 to elicit cell death in fibroblasts. Increasing knowledge of its function, however, has cast doubts on its role. Like p53, the protein contains different isoforms with distinct and sometimes opposite functions. Like other members of the p53 family, p73 protein share the same modular organization consisting of an N-terminal transactivation domain, central sequence-specific DNA-binding domain, and a C-terminal tetramerization domain. However, the p73 gene encodes multiple isoforms varying in their N and C termini. In some cases, the use of a cryptic promoter generates isoforms lacking the transactivation domain located in the N terminus of p73 (deltaNp73 alpha and deltaNp73 beta). The p73 gene also generates several forms with varying C-terminal extensions,TAp73 (p73 alpha, beta, gamma, delta and epsilon). These splicing variants are expressed differently in normal human tissues and cell lines. The p73 gene has been mapped to human chromosome 1p36, a region that is frequently deleted in variety of human cancers including neuroblastoma, colon cancer, and breast cancer. The precise functions of p73 proteins in the organism and the signaling pathways that regulate their activity are still not well established. An interesting recent report shows that p73 is required for p53-dependent apoptosis induced by DNA damage as well as p53-independent apoptosis. These observations and the fact that p73 expression is affected in certain tumors suggest that p73 may function as a tumor suppressor gene. However, p73 deficient mice are not particularly prone to cancer, and only rarely have mutation or inactivation of p73 expression been found in human tumors. On the contrary the deltaNp73 isoforms have oncogenic potential and act in a dominant negative manner against TAp73 as well as p53. The Delta N isoforms of p73 can also protect neurons from apoptosis. Besides like p53, p73 may also play a role in developmental processes. Several lines of evidence show that p73 may play a role in nervous system and immune system development, thus implicating the role of p73 in cellular differentiation.
Thus considering the contradictory role of the various splice variants of p73 protein, IMGENEX has developed an antibody that specifically recognizes the phosphorylated p73 protein which would elucidate the role of p73 in various cellular pathways.
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