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Full-length p73alpha represses drug-induced apoptosis in small cell lung carcinoma cells 总被引:1,自引:0,他引:1
Nyman U Sobczak-Pluta A Vlachos P Perlmann T Zhivotovsky B Joseph B 《The Journal of biological chemistry》2005,280(40):34159-34169
The p73 gene, a member of the p53 family, encodes several variants through differential splicing and use of alternative promoters. At the NH2 terminus, two different promoters generate the full-length and the DeltaN isoforms, with or without the transactivating domain. At the COOH terminus, seven isoforms generated through alternative splicing have been cloned. Previous studies have demonstrated that DeltaNp73 isoforms exert a dominant-negative effect on p73 by blocking their transactivation activity and hence the ability to induce apoptosis. Considerable efforts are made to identify the functional diversity of the COOH-terminal p73 variants. In this study, we found that p73alpha inhibited drug-induced apoptosis in small cell lung carcinoma cells, whereas p73beta promoted it. p73alpha prevented Bax activation, mitochondrial dysfunction, and caspase activation. In addition, p73alpha was also able to reduce apoptosis induced by the BH3-only protein PUMA (p53 up-regulated modulator of apoptosis). Furthermore, we discovered that p73alpha is able to inhibit the pro-apoptotic effect of p73beta, demonstrating the existence of equilibrium between these two p73 isoforms. In conclusion, the reported overexpression of p73alpha in certain tumor types, and our findings that p73alpha exerts anti-apoptotic functions, indicate a potential oncogenic activity for p73. 相似文献
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p73 in apoptosis 总被引:3,自引:0,他引:3
The TP53 tumour-suppressor gene belongs to a family that includes the two recently identified homologues TP63 and TP73. Overexpression of p73 can activate typical p53-responsive genes and induce apoptosis like p53. In addition, activation of p73 has been implicated in apoptotic cell death induced by aberrant cell proliferation and some forms of DNA-damage. These data together with the localization of TP73 on chromosome 1p36, a region frequently deleted in a variety of human cancers, led to the hypothesis that p73 has tumour suppressor activity just like p53. However, despite its proapoptotic activity in vitro, the lack of tumour-formation in p73 knock-out mice and primary human tumour data demonstrating overexpression of wild-type p73 currently argue against p73 being a classical tumour suppressor. Interestingly, in contrast to TP53, TP73 gives rise to a complex pattern of pro- and antiapoptotic p73 isoforms generated by differential splicing and alternative promoter usage. Therefore further insight into the function and regulation of these structurally and functionally diverse p73 proteins is needed to elucidate the role of TP73 for apoptosis and human tumorigenesis. 相似文献
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Fernando Marqu��s-Garc��a Nuria Ferrandiz Rosal��a Fern��ndez-Alonso Laura Gonz��lez-Cano Marta Herreros-Villanueva Manuel Rosa-Garrido Bel��n Fern��ndez-Garc��a Jos�� P. Vaque Margarita M. Marqu��s Mar��a Eugenia Alonso Jos�� Carlos Segovia Javier Le��n Mar��a C. Mar��n 《The Journal of biological chemistry》2009,284(32):21139-21156
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Autoinhibitory regulation of p73 by Delta Np73 to modulate cell survival and death through a p73-specific target element within the Delta Np73 promoter 总被引:4,自引:0,他引:4
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Nakagawa T Takahashi M Ozaki T Watanabe Ki K Todo S Mizuguchi H Hayakawa T Nakagawara A 《Molecular and cellular biology》2002,22(8):2575-2585
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TIP60 represses transcriptional activity of p73beta via an MDM2-bridged ternary complex 总被引:1,自引:0,他引:1
Kim JW Song PI Jeong MH An JH Lee SY Jang SM Song KH Armstrong CA Choi KH 《The Journal of biological chemistry》2008,283(29):20077-20086
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Calpain cleavage regulates the protein stability of p73 总被引:3,自引:0,他引:3
Munarriz E Bano D Sayan AE Rossi M Melino G Nicotera P 《Biochemical and biophysical research communications》2005,333(3):954-960
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