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

• Published in: Cancers Vol. 16; no. 1; p. 229
• Main Authors: Zhang, Jin, Kong, Xiangmudong, Yang, Hee Jung, Mohibi, Shakur, Lucchesi, Christopher August, Zhang, Weici, Chen, Xinbin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024; MDPI
• Subjects: Cancer; Cell adhesion molecules; Cell cycle; Cell growth; Cell migration; cell proliferation; cellular senescence; DNA damage; Embryo fibroblasts; Feedback; Gene expression; Genetic engineering; Genetic translation; Genetically modified organisms; Genomes; Growth; mRNA; Mutants; NINJ2; p53; p53 Protein; Peptides; Proteins; Regeneration; RNA; Senescence; Transcription factors; Translation; Tumor proteins; Tumor suppression; Tumor suppressor genes; Tumorigenesis; Tumors; United States > US; California; cellular senescence; cell proliferation; NINJ2; p53
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16010229

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 that is 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.