Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Curr Cancer Drug Targets. 2009 Dec;9(8):915-30. doi: 10.2174/156800909790192383.
The growth arrest and DNA damage-inducible 45 (Gadd45) proteins are a group of critical signal transducers that are involved in regulations of many cellular functions. Accumulated data indicate that all three Gadd45 proteins (i.e., Gadd45alpha, Gadd45beta, and Gadd45gamma) play essential roles in connecting an upstream sensor module, the transcription Nuclear Factor-kappaB (NF-kappaB), to a transcriptional regulating module, mitogen-activated protein kinase (MAPK). This NF-kappaB-Gadd45(s)-MAPK pathway responds to various kinds of extracellular stimuli and regulates such cell activities as growth arrest, differentiation, cell survival, and apoptosis. Defects in this pathway can also be related to oncogenesis. In the first part of this review, the functions of Gadd45 proteins, and briefly NF-kappaB and MAPK, are summarized. In the second part, the mechanisms by which Gadd45 proteins are regulated by NF-kappaB, and how they affect MAPK activation, are reviewed.
生长停滞和 DNA 损伤诱导蛋白 45（Gadd45）是一组关键的信号转导蛋白，参与调节许多细胞功能。大量数据表明，所有三种 Gadd45 蛋白（即 Gadd45alpha、Gadd45beta 和 Gadd45gamma）在连接上游传感器模块（转录核因子-κB（NF-κB））和转录调节模块（丝裂原激活蛋白激酶（MAPK））方面都发挥着重要作用。这个 NF-κB-Gadd45（s）-MAPK 途径对各种细胞外刺激作出反应，并调节细胞生长停滞、分化、细胞存活和凋亡等细胞活动。该途径的缺陷也可能与肿瘤发生有关。在这篇综述的第一部分，总结了 Gadd45 蛋白的功能，以及简要介绍了 NF-κB 和 MAPK。在第二部分，综述了 NF-κB 调节 Gadd45 蛋白的机制，以及它们如何影响 MAPK 激活。
