Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors

Jin Zhang, Enshun Xu, Cong Ren, Wensheng Yan, Min Zhang, Mingyi Chen, Robert D. Cardiff, Denise M. Imai, Erik Wisner, Xinbin Chen

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

RNA-binding motif protein 38 (Rbm38), also called RNPC1 [RNA-binding region (RNP1, RRM) containing 1], is a target of the p53 family and modulates p53 expression via mRNA translation. To investigate the biological function of Rbm38 in vivo, we generated an Rbm38-null mouse model. We showed that mice deficient in Rbm38 exhibit signs of accelerated aging and are prone to hematopoietic defects and spontaneous tumors. To determine the biological significance of the p53-Rbm38 loop, we showed that Rbm38 deficiency enhances accumulation of p53 induced by ionizing radiation (IR) and sensitizes mice to IR-induced lethality in a p53-dependent manner. Most importantly, Rbm38 deficiency markedly decreases the tumor penetrance in mice heterozygous for p53 via enhanced p53 expression. Interestingly, we found that Rbm38 deficiency shortens the life span of, and promotes lymphomagenesis in, mice deficient in p53. These results provide genetic evidence that Rbm38 is necessary for normal hematopoiesis and for suppressing accelerated aging and tumorigenesis. Thus, the p53-Rbm38 axis might be explored for extending longevity and for tumor suppression.

Original languageEnglish (US)
Pages (from-to)18637-18642
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number52
DOIs
StatePublished - Dec 30 2014

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RNA-Binding Proteins
Neoplasms
Protein Deficiency
Ionizing Radiation
RNA-Binding Motifs
Penetrance
Hematopoiesis
Protein Biosynthesis
Carcinogenesis
RNA

Keywords

  • Aging
  • Hematopoiesis
  • p53
  • Rbm38
  • Tumor suppression

ASJC Scopus subject areas

  • General

Cite this

Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors. / Zhang, Jin; Xu, Enshun; Ren, Cong; Yan, Wensheng; Zhang, Min; Chen, Mingyi; Cardiff, Robert D.; Imai, Denise M.; Wisner, Erik; Chen, Xinbin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 52, 30.12.2014, p. 18637-18642.

Research output: Contribution to journalArticle

Zhang, Jin ; Xu, Enshun ; Ren, Cong ; Yan, Wensheng ; Zhang, Min ; Chen, Mingyi ; Cardiff, Robert D. ; Imai, Denise M. ; Wisner, Erik ; Chen, Xinbin. / Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 52. pp. 18637-18642.
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