Centre for Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK.
EMBO J. 2011 Sep 6;30(20):4261-73. doi: 10.1038/emboj.2011.302.
iASPP, an inhibitory member of the ASPP (apoptosis stimulating protein of p53) family, is an evolutionarily conserved inhibitor of p53 which is frequently upregulated in human cancers. However, little is known about the role of iASPP under physiological conditions. Here, we report that iASPP is a critical regulator of epithelial development. We demonstrate a novel autoregulatory feedback loop which controls crucial physiological activities by linking iASPP to p63, via two previously unreported microRNAs, miR-574-3p and miR-720. By investigating its function in stratified epithelia, we show that iASPP participates in the p63-mediated epithelial integrity program by regulating the expression of genes essential for cell adhesion. Silencing of iASPP in keratinocytes by RNA interference promotes and accelerates a differentiation pathway, which also affects and slowdown cellular proliferation. Taken together, these data reveal iASPP as a key regulator of epithelial homeostasis.
iASPP，凋亡刺激蛋白 p53（apoptosis stimulating protein of p53）家族的抑制成员，是 p53 的一种进化上保守的抑制剂，在人类癌症中经常上调。然而，关于 iASPP 在生理条件下的作用知之甚少。在这里，我们报告 iASPP 是上皮发育的关键调节因子。我们通过两个以前未报道的 microRNAs（miR-574-3p 和 miR-720），证明了一种通过将 iASPP 与 p63 连接起来的新型自反馈回路，控制着通过关键生理活动的关键调节因子。通过研究其在分层上皮中的功能，我们表明 iASPP 通过调节对细胞黏附至关重要的基因的表达，参与 p63 介导的上皮完整性程序。通过 RNA 干扰沉默角质形成细胞中的 iASPP 可促进和加速分化途径，这也会影响和减缓细胞增殖。总之，这些数据揭示了 iASPP 是上皮动态平衡的关键调节因子。
