Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, 301-131, South Korea.
Cell Signal. 2013 Jan;25(1):74-84. doi: 10.1016/j.cellsig.2012.09.009. Epub 2012 Sep 11.
PHD finger protein 20 (PHF20) is a transcription factor, which was originally identified in glioma patients. PHF20 appears to be a novel antigen in glioma, and has also termed glioma-expressed antigen 2. PHF20 is thought to contribute to the development of cancers, including glioblastoma, lung cancer, colon cancer and ovarian cancer. However, little is known about the function of PHF20 in various cancers. Here we report that PHF20 contains two consensus sites for protein kinase B (PKB) phosphorylation (RxRxxS/T). PKB can directly phosphorylate PHF20 on Ser291 in vitro and in vivo. It has been shown that PKB participates in the tumor suppressor p53 regulated gene expression program and has a direct effect on p21 regulation after DNA damage. UV-induced DNA damage results in accumulation of p53 and PKB activation. Interestingly, PKB-mediated PHF20 phosphorylation led to an inhibition of p53 induction following UV treatment, leading to the reduction of p21 transcriptional activity. Using anti PHF20 and anti pPKB (S473) antibodies, these events were mapped in various human cancer tissues. Taken together, these data suggest that PHF20 is a novel substrate for PKB and its phosphorylation by PKB plays an important role in tumorigenesis via regulating of p53 mediated signaling.
PHD 手指蛋白 20（PHF20）是一种转录因子，最初在神经胶质瘤患者中被发现。PHF20 似乎是神经胶质瘤中的一种新抗原，也被称为神经胶质瘤表达抗原 2。PHF20 被认为有助于癌症的发展，包括神经母细胞瘤、肺癌、结肠癌和卵巢癌。然而，关于 PHF20 在各种癌症中的功能知之甚少。在这里，我们报告 PHF20 包含两个蛋白激酶 B（PKB）磷酸化的保守位点（RxRxxS/T）。PKB 可以在体外和体内直接磷酸化 PHF20 的 Ser291 位点。已经表明，PKB 参与肿瘤抑制因子 p53 调节的基因表达程序，并对 DNA 损伤后的 p21 调节有直接影响。UV 诱导的 DNA 损伤导致 p53 的积累和 PKB 的激活。有趣的是，PKB 介导的 PHF20 磷酸化导致 UV 处理后 p53 诱导的抑制，导致 p21 转录活性的降低。使用抗 PHF20 和抗 pPKB（S473）抗体，在各种人类癌症组织中检测到这些事件。总之，这些数据表明 PHF20 是 PKB 的一种新底物，其被 PKB 磷酸化在通过调节 p53 介导的信号转导来促进肿瘤发生中发挥重要作用。
