摘要
哺乳动物细胞对于遗传毒性的刺激会产生一系列应答,如细胞周期阻滞,DNA修复和细胞凋亡等。Gadd45a在DNA损伤诱导的细胞应答中发挥重要作用。细胞内外环境的多种因素在转录水平、转录后水平、翻译后水平等多个层次对Gadd45a进行精确调节。Gadd45a通过与Cdc2相互作用调控细胞周期G2-M检测点,直接抑制Aurora-A激酶参与中心体稳定性的调节,通过G1-S期调控参与维持基因组的稳定性。Gadd45a参与p38/JNK、MAPK、线粒体介导的凋亡途径和NF-κB介导的生存通路调控。
In response to genetic toxins, mammalian cells exhibit complex reactions, including cell cycle arrest, DNA repair and apoptosis. Gadd45a plays very important roles in the DNA damage-induced cellular responses. Gadd45a is regulated at multiple levels, such as transcriptional, post-transcriptional and post-translational levels. Gadd45a interacts with Cdc2 to regulate cell cycle G2-M checkpoint, represses Aurora-A kinase to maintain the stability of centrosome, and regulates the Gj-S checkpoint to participate in the maintenance MEKK4/MTK1 and activates the JNK/p38 signaling of genome stability. pathway that induces Gadd45a interacts with apoptosis. Meanwhile, Gadd45a expression induces Bim dissociation from the cytoskeleton and translocation to mitochondria that induces apoptosis. Some studies showed that Gadd45a could regulate cell survival through NF- κB pathway.
出处
《医学分子生物学杂志》
CAS
CSCD
2007年第5期434-438,共5页
Journal of Medical Molecular Biology
