| 描述 | p53 is a tumor suppressor which acts as an S-phase checkpoint for DNA damage. The gene for p53 is the most commonly mutated gene identified in human cancers. Recently, a new member of the p53 family, p73, has been identified. p73 is structurally homologous to p53 in several regions, including the p53 N-terminal transactivation domain and C-terminal oligomerization domains, as well as the region corresponding to the p53 DNA-binding domain. p73, when overexpressed, can promote p53-like functions, including induction of apoptosis and induction of transcription from p53-responsive promoters such as p21. Despite structural and apparent functional homology, data suggests that these proteins may have distinct functions as well. For example, viral oncoproteins such as Adenovirus E1B 55k and HPV E6, which bind to and thus inactivate p53 during the process of transformation, do not bind to p73. In addition, unlike p53, p73 expression is not induced by DNA damage, i.e., UV irradiation. Several p73 splice variants have been identified, including α (full length), β (missing exon 13), γ (missing exon 11) and δ (missing exons 11, 12, and 13). Two hybrid analysis has shown variable interaction(s) between these isoforms in vitro. Many types of normal, tumor and virally-transformed cell lines express detectable levels of p73; however, the relative expression of p73 isoforms, as well as their functional activity, appears to be differentially regulated in various cell types. p73 alpha and beta isoforms migrate at molecular weights of 80 kD (alpha), 70 kD (beta), respectively. The ER-15 antibody reacts with human p73αandβ. |
