Sui Guangchao, Affar El Bachir, Shi Yujiang, Brignone Chrystelle, Wall Nathan R, Yin Peng, Donohoe Mary, Luke Margaret P, Calvo Dominica, Grossman Steven R, Shi Yang
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Cell. 2004 Jun 25;117(7):859-72. doi: 10.1016/j.cell.2004.06.004.
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.
阴阳1（YY1）是一种在发育过程中起关键作用的转录因子。然而，YY1的全部功能和作用机制仍不清楚。我们发现，在体内，由于p53泛素化减少，YY1缺失会导致p53积累。相反，YY1过表达会刺激p53泛素化和降解。重要的是，重组YY1在体外足以诱导Hdm2介导的p53多聚泛素化，这表明YY1的这一功能独立于其转录活性。我们确定了YY1与Hdm2和p53之间直接的物理相互作用，并表明YY1调节p53泛素化的基础是其促进Hdm2-p53相互作用的能力。重要的是，肿瘤抑制因子p14ARF会破坏Hdm2-YY1相互作用，这对YY1调节p53很重要。综上所述，这些发现确定YY1是Hdm2在调节p53稳态中的潜在辅助因子，并提示YY1在肿瘤发生中可能发挥作用。
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