The Beatson Institute for Cancer Research, Garscube Estate, Glasgow, UK.
EMBO J. 2012 Jan 18;31(2):471-80. doi: 10.1038/emboj.2011.402. Epub 2011 Nov 8.
In addition to acting as a transcriptional cofactor for p53, ASPP1 has been shown to function in the cytoplasm to regulate the nuclear localization and activity of YAP/TAZ. We show here that the ability of ASPP1 to activate YAP results in the decreased expression of LATS2, which lowers the ability of p53 to induce p21, cell-cycle arrest and senescence. ASPP1 expression peaks in S-phase, and down-regulation of ASPP1 leads to a reduction in DNA synthesis and enhanced senescence in response to drugs that impede DNA replication. These activities of cytoplasmic ASPP1 in opposing p53-mediated p21 expression are in contrast to the role of nuclear ASPP1 in cooperating with p53 to induce the expression of apoptotic target genes, and may help to dampen p53 activity in normal cells.
除了作为 p53 的转录共激活因子外，ASPP1 已被证明在细胞质中发挥作用，以调节 YAP/TAZ 的核定位和活性。我们在这里表明，ASPP1 激活 YAP 的能力导致 LATS2 的表达降低，从而降低 p53 诱导 p21、细胞周期停滞和衰老的能力。ASPP1 的表达在 S 期达到峰值，下调 ASPP1 会导致 DNA 合成减少，并增强对阻碍 DNA 复制的药物的衰老反应。细胞质 ASPP1 的这些活性与核 ASPP1 与 p53 合作诱导凋亡靶基因表达的作用相反，并且可能有助于在正常细胞中抑制 p53 活性。
