日本山口大學(xué)研究人員日前報(bào)告說(shuō),，他們發(fā)現(xiàn)由兩個(gè)蛋白質(zhì)結(jié)合而成的一種復(fù)合體與癌細(xì)胞的形成和增殖相關(guān),，如果能找到切斷兩者結(jié)合的物質(zhì)，就有望開發(fā)出治療癌癥的新藥,。
發(fā)現(xiàn)蛋白質(zhì)復(fù)合體與癌細(xì)胞增殖相關(guān)的是山口大學(xué)研究生院教授中井彰率領(lǐng)的研究小組,。據(jù)研究人員介紹,，此前的研究表明，名為“熱休克轉(zhuǎn)錄因子1”的蛋白質(zhì)能使細(xì)胞內(nèi)蛋白質(zhì)的數(shù)量和質(zhì)量維持在一定水平,，這種作用在癌細(xì)胞內(nèi)尤其顯著,。
中井等人在此項(xiàng)新研究中發(fā)現(xiàn),，“熱休克轉(zhuǎn)錄因子1”必須要與另一種蛋白質(zhì)“復(fù)制蛋白A1”相結(jié)合,，才能發(fā)揮作用。他們通過(guò)基因操作,，培養(yǎng)出這兩種蛋白質(zhì)無(wú)法結(jié)合在一起的人類癌細(xì)胞,，然后移植到實(shí)驗(yàn)鼠體內(nèi)，結(jié)果發(fā)現(xiàn)癌細(xì)胞增殖受遏制,，無(wú)法形成腫瘤,。
中井彰指出：“如果能找到阻礙這兩種蛋白質(zhì)結(jié)合的物質(zhì)，就有望開發(fā)出對(duì)正常細(xì)胞幾乎不產(chǎn)生影響,，而只遏制癌細(xì)胞增殖的劃時(shí)代新藥,。”相關(guān)論文已發(fā)表在8月30日出版的《分子細(xì)胞》網(wǎng)絡(luò)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.
