[转移帖]法研究发现一种病毒蛋白质可转变为宫颈癌杀手
原帖由论坛会员mchris发表于 2008-12-24 19:48 |新华网巴黎12月17日电（记者李学梅）法国斯特拉斯堡路易·巴斯德大学的研究人员日前发现，一种导致宫颈癌的蛋白质经过极其微小的变异，可以转而抑制这种癌症的扩散，这一成果将有助于科学家们研制治疗宫颈癌的新药。
路易·巴斯德大学的科研人员在17日出版的英国《致癌基因》杂志电子版上报告说，全世界每年有50万妇女罹患宫颈癌，其中80％生活在发展中国家。这种病主要通过性行为传播，而导致它的罪魁祸首正是人乳头状瘤病毒（ＨＰＶ）。
据介绍，ＨＰＶ病毒会产生两种基因蛋白质，分别被命名为Ｅ6和Ｅ7，科研人员发现，Ｅ6导致癌细胞的增殖，但当它发生变异以后，却转而开始抑制肿瘤的生成。研究小组认为，虽然这种变异微不足道，但却能彻底改变Ｅ6的性质。
路易·巴斯德大学表示，目前治疗宫颈癌的主要方法是接种疫苗，不过它的价格会令一些发展中国家的患者望而却步。此外，对于那些已经患病的女性来说，疫苗也无济于事，因此，他们希望利用这一发现，研究出能治疗宫颈癌的特效药。
Rojjer发表于 2008-12-27 20:41：
A single-codon mutation converts HPV16 E6 oncoprotein into a potential tumor suppressor, which induces p53-dependent senescence of HPV-positive HeLa cervical cancer cells
T Ristriani1, S Fournane1, G Orfanoudakis1, G Travé1 and M Masson1
1Equipe Oncoprotéines, CNRS-UMR 7175, ESBS, Boulevard Sébastien Brant, Illkirch, Bas-Rhin, France
Correspondence: Dr M Masson, Equipe Oncoprotéines, CNRS-UMR 7175, ESBS, Boulevard Sébastien Brant, BP10413, Illkirch, Bas-Rhin 67412, France. E-mail: masson@esbs.u-strasbg.fr; Dr G Travé, Equipe Oncoprotéines, CNRS-UMR 7175, ESBS, Boulevard Sébastien Brant, BP10413, Illkirch, Bas-Rhin 67412, France. E-mail: gtrave@titus.u-strasbg.fr
Received 21 August 2008; Revised 29 September 2008; Accepted 21 October 2008; Published online 17 November 2008.
High-risk mucosal human papillomaviruses (HPV), mainly HPV16 and HPV18, are implicated in cervical carcinogenesis. HPV16 E6 oncoprotein binds and often targets for degradation numerous cell proteins, including the tumor suppressor p53 and several PDZ domain proteins. Here, we show that a single-point mutation, F47R, is sufficient to convert the HPV16 E6 oncoprotein into a suppressor of HPV-positive HeLa cervical cancer cells proliferation. The E6 F47R mutant is defective for polyubiquitination and subsequent degradation of p53. When expressed in HPV-positive cervical cancer cells, E6 F47R acts as a dominant negative mutant by counteracting the p53 degradation activity of endogenous E6 and restoring high p53 protein levels. Moreover, the prolonged expression of E6 F47R leads to suppression of HeLa cells proliferation through the induction of premature senescence. This phenotype is independent on the PDZ-binding activity of E6. F47R-senescent HeLa cells exhibit a sustained expression of p53, hMDM2 and p21CIP proteins and a reduced expression of endogenous HPV18 E6 protein. Finally, small interfering RNAs directed against p53 counteract the effect of E6 F47R expression, indicating that E6 F47R-induced cellular senescence is strongly dependent on p53 signaling pathway.
Keywords: human papillomavirus, cervical cancer, E6 oncoprotein, senescence, p53 protein
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