Conforti Franco, Yang Ai Li, Agostini Massimiliano, Rufini Alessandro, Tucci Paola, Nicklison-Chirou Maria Victoria, Grespi Francesca, Velletri Tania, Knight Richard A, Melino Gerry, Sayan Berna S
University of Southampton, Cancer Sciences Unit, Somers Cancer Research Building, Southampton, UK.
Aging (Albany NY). 2012 Mar;4(3):202-5. doi: 10.18632/aging.100441.
The transcription factor p73 belongs to the p53 family of tumour suppressors and similar to other family members, transcribed as different isoforms with opposing pro- and anti-apoptotic functions. Unlike p53, p73 mutations are extremely rare in cancers. Instead, the pro-apoptotic activities of transcriptionally active p73 isoforms are commonly inhibited by over-expression of the dominant negative p73 isoforms. Therefore the relative ratio of different p73 isoforms is critical for the cellular response to a chemotherapeutic agent. Here, we analysed the expression of N-terminal p73 isoforms in cell lines and mouse tissues. Our data showed that the transcriptionally competent TAp73 isoform is abundantly expressed in cancer cell lines compared to the dominant negative ΔNp73 isoform. Interestingly, we detected higher levels of ΔNp73 in some mouse tissues, suggesting that ΔNp73 may have a physiological role in these tissues.
转录因子p73属于肿瘤抑制因子p53家族，与其他家族成员相似，它转录生成具有相反促凋亡和抗凋亡功能的不同异构体。与p53不同，p73突变在癌症中极为罕见。相反，转录活性p73异构体的促凋亡活性通常会被显性负性p73异构体的过表达所抑制。因此，不同p73异构体的相对比例对于细胞对化疗药物的反应至关重要。在此，我们分析了细胞系和小鼠组织中N端p73异构体的表达。我们的数据表明，与显性负性ΔNp73异构体相比，转录活性TAp73异构体在癌细胞系中大量表达。有趣的是，我们在一些小鼠组织中检测到较高水平的ΔNp73，这表明ΔNp73可能在这些组织中具有生理作用。
