p53 Tumor Suppressor Pathway

真核生物的基因组不断面临着外源性和外源性基因破坏的威胁， 内源性诱变剂因此，哺乳动物细胞已经进化出一个复杂的防御网络 来维持基因组的稳定性p53处于这些防御途径的十字路口。我们 研究罕见的基因组不稳定性和/或过早衰老疾病，例如，布鲁姆，沃纳， Rothmund-Thomson和Li-Fraumeni Syndrome，以深入了解p53在一般性 人口例如，p53介导的细胞凋亡也受人RecQ家族的调节。 DNA解旋酶。p53还促进DNA修复途径。我们还发现 p53的转录辅因子，即，ING 2 -5，增强细胞中p53效应子功能 周期检查点、凋亡和衰老。ING 4抑制细胞扩散， 通过与新的结合伴侣liprin alpha 1相互作用进行迁移。新的剪接变体 此外，还发现了ING 4。我们正在继续研究p53介导的复制衰老 由ING家族蛋白或POT 1和p53亚型调节， 消耗

The eukaryote genome constantly faces the threat of damage from exogenous and endogenous mutagens. Mammalian cells, therefore, have evolved an intricate network of defenses to maintain genomic stability. p53 is at the crossroads of these defense pathways. We investigate rare genomic instability and/or premature aging diseases, e.g., Bloom, Werner, Rothmund-Thomson, and Li-Fraumeni Syndromes, to gain insight into p53 function in the general population. For example, p53-mediated apoptosis is also modulated by the human RecQ family of DNA helicases. p53 also facillitates DNA repair pathways. We have also discovered transcriptional cofactors of p53, i.e., ING2-5, that enhance p53 effector functions in cell cycle checkpoints, apoptosis, and senescence. ING4 suppresses cell spreading and cell migration by interacting with a novel binding partner, liprin alpha1. Novel splice variants of ING4 have also been discovered. We are continuing to study p53-mediated replicative senescence modulated by either ING family proteins or by POT1 and p53 isoforms that govern telomere attrition.