近日,,Stem Cells雜志上發(fā)表了中國科學(xué)院遺傳與發(fā)育生物學(xué)研究所戴建武博士研究組的研究成果。研究發(fā)現(xiàn),,OCT4B-265在基因毒性壓力下(例如絲裂霉素C,,多柔比星處理或者紫外輻射)表達(dá)上調(diào)。分子和生物化學(xué)研究表明,,OCT4B-265對基因毒性損傷的反應(yīng)只出現(xiàn)在一些具有干細(xì)胞特性的細(xì)胞中,。在基因毒性下,OCT4B-265可以促進(jìn)細(xì)胞凋亡,,并且這種作用是依賴于p53,。
OCT4是一個(gè)在胚胎發(fā)育過程中起重要作用的關(guān)鍵轉(zhuǎn)錄因子。人的OCT4基因至少可以產(chǎn)生四個(gè)蛋白異構(gòu)體,,分別是OCT4A,,OCT4B-265,OCT4B-190和OCT4B-164,。其中,,OCT4A對維持干細(xì)胞特性起作用,也是被研究最多的一種異構(gòu)體,。之前的研究證明,,OCT4B-190可以在細(xì)胞應(yīng)激過程中發(fā)揮作用,而OCT4B的其他異構(gòu)體的功能還不是很清楚,。
研究結(jié)果揭示了OCT4B蛋白的新功能,,對于了解OCT4基因蛋白質(zhì)種類的多樣性及功能的復(fù)雜性具有重要的參考價(jià)值。同時(shí),,OCT4B-265蛋白在預(yù)防干細(xì)胞基因毒性損傷方面可能會(huì)有重要的應(yīng)用前景,。(生物谷Bioon.com)
doi:10.1002/stem.1034
PMC:
PMID:
The Novel Function of OCT4B Isoform-265 in Genotoxic Stress
Yuan Gao, Jianshu Wei, Jin Han, Xia Wang, Guannan Su, Yannan Zhao, Bing Chen, Zhifeng Xiao, Jiani Cao, Jianwu Dai
OCT4 is a key transcription factor in maintaining the pluripotency and self-renewal of embryonic stem (ES) cells. Human OCT4 gene can generate three mRNA isoforms (OCT4A, OCT4B and OCT4B1) by alternative splicing and four protein isoforms (OCT4A, OCT4B-265, OCT4B-190 and OCT4B-164) by alternative splicing or alternative translation initiation. OCT4A is a transcription factor responsible for the stemness of ES cells, while the function of OCT4B protein isoforms is still not clear. We have previously reported that OCT4B-190 functioned in cell stress response. Here we present another product of OCT4 gene, OCT4B-265, is up-regulated under genotoxic stress in stem cells, and it may function in stress response through p53 signaling pathway. This work gives an insight into the novel function of OCT4B protein isoforms and helps us to understand the complex expression patterns and biological functions of OCT4 gene.