A Glance of p53 Functions in Brain Development, Neural Stem Cells, and Brain Cancer.
A Glance of p53 Functions in Brain Development, Neural Stem Cells, and Brain Cancer.
复制标题
DOI：
10.3390/biology9090285
复制
发表时间：
2020-09-11
期刊：
影响因子：
4.2
通讯作者：
Williams-Villalobo AE
中科院分区：
文献类型：
--
作者：
Xiong Y;Zhang Y;Xiong S;Williams-Villalobo AE
p53是研究最深入的肿瘤抑制因子之一。它通过转录调节广泛的基因来调节一系列细胞事件，包括DNA损伤修复、细胞周期停滞、衰老、凋亡、铁凋亡、自噬和代谢重塑，这些都是发育和癌症的基础。本文就p53在脑发育中的作用、神经干细胞的调控以及p53在胶质瘤中的失活机制作一综述。p53缺失或p53突变小鼠表现出雌性偏性露脑畸形，这可能是由于X染色体失活失败和/或胚胎相关基因表达所致。氧化细胞状态、PI 3 K/Akt信号传导增加、ID 1升高和代谢都与p53丢失诱导的神经发生有关。然而，p53也被证明可以促进神经元分化。此外，p53突变经常在脑肿瘤，特别是胶质母细胞瘤中发现。脑肿瘤细胞中p53失活的潜在机制包括p53蛋白稳定性、基因表达和反式激活潜力的破坏以及p53基因丢失或突变。p53功能的丧失和突变型p53功能的获得都与脑发育和肿瘤发生有关。进一步了解p53在大脑中的作用可能会为大脑发育综合征和癌症提供治疗见解。
p53 is one of the most intensively studied tumor suppressors. It transcriptionally regulates a broad range of genes to modulate a series of cellular events, including DNA damage repair, cell cycle arrest, senescence, apoptosis, ferroptosis, autophagy, and metabolic remodeling, which are fundamental for both development and cancer. This review discusses the role of p53 in brain development, neural stem cell regulation and the mechanisms of inactivating p53 in gliomas. p53 null or p53 mutant mice show female biased exencephaly, potentially due to X chromosome inactivation failure and/or hormone-related gene expression. Oxidative cellular status, increased PI3K/Akt signaling, elevated ID1, and metabolism are all implicated in p53-loss induced neurogenesis. However, p53 has also been shown to promote neuronal differentiation. In addition, p53 mutations are frequently identified in brain tumors, especially glioblastomas. Mechanisms underlying p53 inactivation in brain tumor cells include disruption of p53 protein stability, gene expression and transactivation potential as well as p53 gene loss or mutation. Loss of p53 function and gain-of-function of mutant p53 are both implicated in brain development and tumor genesis. Further understanding of the role of p53 in the brain may provide therapeutic insights for brain developmental syndromes and cancer.
登录
查看更多内容
影响因子：
4
作者：
Angeloni, SV;Martin, MB;Saceda, M
通讯作者：
Saceda, M
影响因子：
7.9
作者：
Hutson, Dillion D.;Gurrala, Rakesh;Lindsey, Sarah H.
通讯作者：
Lindsey, Sarah H.
影响因子：
8.8
作者：
Delbridge, Alex R. D.;Kueh, Andrew J.;Voss, Anne K.
通讯作者：
Voss, Anne K.
影响因子：
4.8
作者：
Berger, Crystal E.;Qian, Yingjuan;Chen, Xinbin
通讯作者：
Chen, Xinbin
影响因子：
5.3
作者：
Forsberg, Kirsi;Wuttke, Anja;Di Giovanni, Simone
通讯作者：
Di Giovanni, Simone