YY1 binding to a subset of p53 DNA-target sites regulates p53-dependent transcription.

YY1 binding to a subset of p53 DNA-target sites regulates p53-dependent transcription.
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DOI:
10.1016/j.bbrc.2004.04.065
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发表时间:
2004-05
影响因子:
3.1
通讯作者:
T. Yakovleva;L. Kolesnikova;V. Vukojević;I. Gileva;K. Tan-No;M. Austen;B. Lüscher;T. Ekström;L. Terenius;G. Bakalkin
T. Yakovleva;L. Kolesnikova;V. Vukojević;I. Gileva;K. Tan-No;M. Austen;B. Lüscher;T. Ekström;L. Terenius;G. Bakalkin
中科院分区:
生物学4区
文献类型:
--
作者:
T. Yakovleva;L. Kolesnikova;V. Vukojević;I. Gileva;K. Tan-No;M. Austen;B. Lüscher;T. Ekström;L. Terenius;G. Bakalkin

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肿瘤抑制蛋白p53通过与特定的DNA靶位点结合来调节基因转录。我们在这里证明,这些网站的一个子集是由另一个DNA结合因子的目标。结合特异性,与特异性抗体的反应性,和纯化蛋白的实验确定该因子为多功能转录调节因子YY 1。YY1核心结合序列ACAT存在于分别调节生长停滞和DNA修复的p21和GADD 45基因中的p53半结合位点的中心,但在对细胞凋亡至关重要的Bax基因中不存在。在转染实验中,YY1抑制p53激活的转录从p53结合位点,包含ACAT序列。YY 1和p53共定位在经历凋亡的PC12细胞中的核仁周围和离散的核结构域中。YY1可能减弱p53靶基因亚组的p53依赖性转录,这可能与指导细胞在p53激活后生长停滞或凋亡有关。
The tumor suppressor protein p53 regulates gene transcription through binding to specific DNA-target sites. We here demonstrate that a subset of these sites is targeted by another DNA-binding factor. Binding specificity, reactivity with specific antibodies, and experiments with purified protein identified the factor as the multifunctional transcription regulator YY1. The YY1 core binding sequence ACAT is present in the center of p53-half-binding sites in the p21 and GADD45 genes regulating growth arrest and DNA repair, respectively, but is absent in those of the Bax gene critical for apoptosis. In transfection experiments YY1 inhibits p53-activated transcription from the p53-binding site that contains the ACAT sequence. YY1 and p53 are colocalized around the nucleoli and in discrete nuclear domains in PC12 cells undergoing apoptosis. YY1 might attenuate p53-dependent transcription from a subset of p53-target genes and this may be relevant for directing cells either to growth arrest or apoptosis upon p53 activation.