日本山口大学研究人员日前报告说，他们发现由两个蛋白质结合而成的一种复合体与癌细胞的形成和增殖相关，如果能找到切断两者结合的物质，就有望开发出治疗癌症的新药。
发现蛋白质复合体与癌细胞增殖相关的是山口大学研究生院教授中井彰率领的研究小组。据研究人员介绍，此前的研究表明，名为“热休克转录因子1”的蛋白质能使细胞内蛋白质的数量和质量维持在一定水平，这种作用在癌细胞内尤其显著。
中井等人在此项新研究中发现，“热休克转录因子1”必须要与另一种蛋白质“复制蛋白A1”相结合，才能发挥作用。他们通过基因操作，培养出这两种蛋白质无法结合在一起的人类癌细胞，然后移植到实验鼠体内，结果发现癌细胞增殖受遏制，无法形成肿瘤。
中井彰指出：“如果能找到阻碍这两种蛋白质结合的物质，就有望开发出对正常细胞几乎不产生影响，而只遏制癌细胞增殖的划时代新药。”相关论文已发表在8月30日出版的《分子细胞》网络版上。（生物谷Bioon.com）
doi:10.1016/j.molcel.2012.07.026
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RPA Assists HSF1 Access to Nucleosomal DNA by Recruiting Histone Chaperone FACT
Mitsuaki Fujimoto, Eiichi Takaki, Ryosuke Takii, Ke Tan, Ramachandran Prakasam, Naoki Hayashida, Shun-ichiro Iemura, Tohru Natsume, Akira Nakai
Transcription factor access to regulatory elements is prevented by the nucleosome. Heat shock factor 1 (HSF1) is a winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements, but mechanisms of HSF1 access are not well known in mammalian cells. Here, we show the physical interaction between the wing motif of human HSF1 and replication protein A (RPA), which is involved in DNA metabolism. Depletion of RPA1 abolishes HSF1 access to the promoter of HSP70 in unstressed condition and delays its rapid activation in response to heat shock. The HSF1-RPA complex leads to preloading of RNA polymerase II and opens the chromatin structure by recruiting a histone chaperone, FACT. Furthermore, this interaction is required for melanoma cell proliferation. These results provide a mechanism of constitutive HSF1 access to nucleosomal DNA, which is important for both basal and inducible gene expression.
