Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner

Significance Nerve injury-induced protein 1 (Ninj1), a p53 target, forms a feedback loop with p53 by repressing p53 translation. Here, we show that cell growth was enhanced by Ninj1 deficiency in cells carrying a mutant p53, but inhibited in cells carrying a WT p53. We also show that in WT p53 background, Ninj1- deficient mice were prone to systemic inflammation, but not to spontaneous tumors. Importantly, loss of Ninj1 altered lifespan and tumor susceptibility in mutant p53 and p53 -null mice. Taken together, our results reveal a critical role of Ninj1 in p53-dependent tumor suppression and the Ninj1–p53 loop may be explored as a potential therapeutic target for the treatment of inflammatory diseases and cancers.