Ghafouri-Fard Soudeh, Taheri Mohammad, Baniahmad Aria
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19835-35511, Iran.
Institute of Human Genetics, Jena University Hospital, 07743 Jena, Germany.
Cancers (Basel). 2022 Jun 24;14(13):3107. doi: 10.3390/cancers14133107.
The Inhibitor of Growth (ING) proteins are a group of tumor suppressors with five conserved genes. A common motif of ING factors is the conserved plant homeodomain (PHD), with which they bind to chromatin as readers of the histone mark trimethylated histone H3 (H3K4me3). These genes often produce several protein products through alternative splicing events. Interestingly, ING1 and ING2 participate in the establishment of the repressive mSIN3a-HDAC complexes, whereas ING3, ING4, and ING5 are associated with the activating HAT protein complexes. In addition to the modulation of chromatin's structure, they regulate cell cycle transition, cellular senescence, repair of DNA damage, apoptosis, and angiogenic pathways. They also have fundamental effects on regulating cellular senescence in cancer cells. In the current review, we explain their role in cellular senescence based on the evidence obtained from cell line and animal studies, particularly in the context of cancer.
生长抑制因子（ING）蛋白是一组具有五个保守基因的肿瘤抑制因子。ING因子的一个共同基序是保守的植物同源结构域（PHD），它们通过该结构域作为组蛋白标记三甲基化组蛋白H3（H3K4me3）的识别蛋白与染色质结合。这些基因通常通过可变剪接事件产生几种蛋白质产物。有趣的是，ING1和ING2参与抑制性mSIN3a-HDAC复合物的形成，而ING3、ING4和ING5与激活型HAT蛋白复合物相关。除了调节染色质结构外，它们还调控细胞周期转换、细胞衰老、DNA损伤修复、细胞凋亡和血管生成途径。它们对调节癌细胞中的细胞衰老也有重要作用。在本综述中，我们根据从细胞系和动物研究中获得的证据，特别是在癌症背景下，解释它们在细胞衰老中的作用。
