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

Author:
Zhang, Jin, Xu, Enshun, Ren, Cong, Yan, Wensheng, Zhang, Min, Chen, Mingyi, Cardiff, Robert D., Imai, Denise M., Wisner, Erik, Chen, Xinbin
Source:
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.52 pp. 18637-18642
ISSN:
0027-8424
Subject:
carcinogenesis, hematopoiesis, longevity, messenger RNA, mice, neoplasms, translation (genetics)
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.
Agid:
2302829