生物谷报道:阴阳因子是机体内重要的调节因子,既可作为转录抑制子,也可以是转录激活子,也可以作为起始子。自从1996被发现以来,一直成为研究热点。最新一期Cell报道,它还能下调P53,表明YY1在肿瘤,细胞凋亡中也能发挥重要作用。
Yin Yang 1 (YY1) is a transcription factor that plays an essential role in development. However, the full spectrum of YY1's functions and mechanism of action remains unclear. We find that YY1 ablation results in p53 accumulation due to a reduction of p53 ubiquitination in vivo. Conversely, YY1 overexpression stimulates p53 ubiquitination and degradation. Significantly, recombinant YY1 is sufficient to induce Hdm2-mediated p53 polyubiquitination in vitro, suggesting that this function of YY1 is independent of its transcriptional activity. We identify direct physical interactions of YY1 with Hdm2 and p53 and show that the basis for YY1-regulating p53 ubiquitination is its ability to facilitate Hdm2-p53 interaction. Importantly, the tumor suppressor p14ARF compromises the Hdm2-YY1 interaction, which is important for YY1 regulation of p53. Taken together, these findings identify YY1 as a potential cofactor for Hdm2 in the regulation of p53 homeostasis and suggest a possible role for YY1 in tumorigenesis.
原文见:
Yin Yang 1 Is a Negative Regulator of p53
Guangchao Sui, El Bachir Affar, Yujiang Shi, Chrystelle Brignone, Nathan R. Wall, Peng Yin, Mary Donohoe, Margaret P. Luke, Dominica Calvo, Steven R. Grossman, and Yang Shi
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