Ninjurin1, a target of p53, regulates p53 expression and p53-dependent cell survival, senescence, and radiation-induced mortality

Seong Jun Cho, Andrea Rossi, Yong Sam Jung, Wensheng Yan, Gang Liu, Jin Zhang, Min Zhang, Xinbin Chen

Research output: Contribution to journalArticle

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Abstract

The tumor suppressor protein p53 plays a crucial role in coordinating cellular processes, such as cell cycle arrest, apoptosis, and senescence. The nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a homophilic adhesion molecule and involved in nerve regeneration. Interestingly, Ninj1 is found to be overexpressed in human cancer, but its role in tumorigenesis is not clear. Here, we found that Ninj1 is transcriptionally regulated by p53 and can be induced by DNA damage in a p53-dependent manner. We also found that knockout or knockdown of Ninj1 increases p53 expression potentially through enhanced p53 mRNA translation. In addition, we found that Ninj1 deficiency suppresses cell proliferation but enhances apoptosis and premature senescence in a p53-dependent manner. Consistent with this, we found that mice heterozygous in ninj1 are hypersensitive to ionizing radiation-induced lethality, along with increased expression of p53 in thymus. Taken together, we provided evidence that Ninj1 is a p53 target and modulates p53 mRNA translation and p53-dependent premature senescence, cell proliferation, apoptosis, and radiationinduced mortality in vitro and in vivo. Thus, we postulate that as a membrane adhesion molecule, Ninj1 is an ideal target to regulate p53 activity via the p53-Ninj1 loop.

Original languageEnglish (US)
Pages (from-to)9362-9367
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number23
DOIs
StatePublished - Jun 4 2013

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Cell Aging
Cell Survival
Protein Biosynthesis
Radiation
Apoptosis
Mortality
Cell Proliferation
Tumor Suppressor Protein p53
Nerve Regeneration
Cell Cycle Checkpoints
Ionizing Radiation
Thymus Gland
DNA Damage
Carcinogenesis
Membranes
Wounds and Injuries
Neoplasms
Proteins

Keywords

  • Cellular senescence
  • Radiosensitivity

ASJC Scopus subject areas

  • General

Cite this

Ninjurin1, a target of p53, regulates p53 expression and p53-dependent cell survival, senescence, and radiation-induced mortality. / Cho, Seong Jun; Rossi, Andrea; Jung, Yong Sam; Yan, Wensheng; Liu, Gang; Zhang, Jin; Zhang, Min; Chen, Xinbin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 23, 04.06.2013, p. 9362-9367.

Research output: Contribution to journalArticle

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