文章：

Ninjurin 2：一种细胞黏附分子及p53靶点，在野生型p53中调控生长抑制，在突变型p53中调控生长促进

Ninjurin 2, a Cell Adhesion Molecule and a Target of p53, Modulates Wild-Type p53 in Growth Suppression and Mutant p53 in Growth Promotion

原文发布日期：4 January 2024

DOI: 10.3390/cancers16010229

类型: Article

开放获取: 是

英文摘要：

The nerve injury-induced protein 1 (NINJ1) and NINJ2 constitute a family of homophilic adhesion molecules and are involved in nerve regeneration. Previously, we showed that NINJ1 and p53 are mutually regulated and the NINJ1-p53 loop plays a critical role in p53-dependent tumor suppression. However, the biology of NINJ2 has not been well-explored. By using multiple in vitro cell lines and genetically engineered mouse embryo fibroblasts (MEFs), we showed thatNINJ2is induced by DNA damage in a p53-dependent manner. Moreover, we found that the loss of NINJ2 promotes p53 expression via mRNA translation and leads to growth suppression in wild-type p53-expressing MCF7 and Molt4 cells and premature senescence in MEFs in a wild-type p53-dependent manner. Interestingly, NINJ2 also regulates mutant p53 expression, and the loss of NINJ2 promotes cell growth and migration in mutant p53-expressing MIA-PaCa2 cells. Together, these data indicate that the mutual regulation between NINJ2 and p53 represents a negative feedback loop, and the NINJ2-p53 loop has opposing functions in wild-type p53-dependent growth suppression and mutant p53-dependent growth promotion.

摘要翻译： 

神经损伤诱导蛋白1（NINJ1）与NINJ2构成同嗜性黏附分子家族，参与神经再生过程。既往研究表明，NINJ1与p53存在双向调控关系，且NINJ1-p53调控环路在p53依赖性肿瘤抑制中发挥关键作用。然而，NINJ2的生物学功能尚未得到充分阐释。本研究通过多种体外细胞系及基因工程小鼠胚胎成纤维细胞（MEFs）模型发现，NINJ2的表达可在p53依赖性途径中被DNA损伤诱导激活。进一步研究发现，在表达野生型p53的MCF7和Molt4细胞中，NINJ2缺失通过促进p53 mRNA翻译上调p53表达，进而抑制细胞生长；在MEFs中则引发p53依赖性早衰现象。值得注意的是，NINJ2同样参与调控突变型p53表达，在表达突变型p53的MIA-PaCa2细胞中，NINJ2缺失可促进细胞生长与迁移。综上，本研究揭示NINJ2与p53构成负反馈调控环路，该环路在野生型p53依赖性生长抑制与突变型p53依赖性生长促进中呈现相反的双重调控功能。

原文链接：

Ninjurin 2, a Cell Adhesion Molecule and a Target of p53, Modulates Wild-Type p53 in Growth Suppression and Mutant p53 in Growth Promotion