维持平衡：表观遗传调控的肿瘤抑制作用。

Keep-ING balance: tumor suppression by epigenetic regulation.

机构信息

Dept. of Pediatric Oncology/Hematology, Charité-Medical School Berlin, Germany.

Department of Biochemistry & Molecular Biology, Faculty of Medicine, University of Calgary, Canada.

出版信息

FEBS Lett. 2014 Aug 19;588(16):2728-42. doi: 10.1016/j.febslet.2014.03.011. Epub 2014 Mar 14.

DOI:10.1016/j.febslet.2014.03.011

PMID:24632289

Abstract

Cancer cells accumulate genetic and epigenetic changes that alter gene expression to drive tumorigenesis. Epigenetic silencing of tumor suppressor, cell cycle, differentiation and DNA repair genes contributes to neoplastic transformation. The ING (inhibitor of growth) proteins (ING1-ING5) have emerged as a versatile family of growth regulators, phospholipid effectors, histone mark sensors and core components of HDAC1/2 - and several HAT chromatin-modifying complexes. This review will describe the characteristic pathways by which ING family proteins differentially affect the Hallmarks of Cancer and highlight the various epigenetic mechanisms by which they regulate gene expression. Finally, we will discuss their potentials as biomarkers and therapeutic targets in epigenetic treatment strategies.

摘要

癌细胞积累遗传和表观遗传变化，改变基因表达以驱动肿瘤发生。肿瘤抑制因子、细胞周期、分化和 DNA 修复基因的表观遗传沉默导致肿瘤转化。ING（生长抑制剂）蛋白（ING1-ING5）已成为一种多功能的生长调节剂家族、磷脂效应物、组蛋白标记传感器以及 HDAC1/2 和几种 HAT 染色质修饰复合物的核心组件。本综述将描述 ING 家族蛋白通过不同途径影响癌症特征的特征性途径，并强调它们调节基因表达的各种表观遗传机制。最后，我们将讨论它们作为表观遗传治疗策略中的生物标志物和治疗靶点的潜力。