Abstract
Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often altered in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice by shortening lifespan, altering tumor incidence, and promoting T-cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T-cell development. Furthermore, Rbm38 was required for Pten expression via stabilization of Pten mRNA through an AU-rich element in its 3'UTR. Our results suggest that Rbm38 controls T-cell lymphomagenesis by jointly modulating mutant p53 and Pten, with possible therapeutic implications for treating T-cell malignancies. Significance: An RNA-binding protein controls T-cell lymphomagenesis by jointly modulating mutant p53 and PTEN, with possible therapeutic implications for treating T-cell malignancies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1511-1521 |
| Number of pages | 11 |
| Journal | Cancer Research |
| Volume | 78 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2018 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Genetic ablation of Rbm38 promotes lymphomagenesis in the context of mutant p53 by downregulating PTEN. / Zhang, Jin; Xu, Enshun; Ren, Cong; Yang, Hee Jung; Zhang, Yanhong; Sun, Wenqiang; Kong, Xiangmudong; Zhang, Weici; Chen, Mingyi; Huang, Eric C; Chen, Xinbin.
In: Cancer Research, Vol. 78, No. 6, 15.03.2018, p. 1511-1521.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic ablation of Rbm38 promotes lymphomagenesis in the context of mutant p53 by downregulating PTEN
AU - Zhang, Jin
AU - Xu, Enshun
AU - Ren, Cong
AU - Yang, Hee Jung
AU - Zhang, Yanhong
AU - Sun, Wenqiang
AU - Kong, Xiangmudong
AU - Zhang, Weici
AU - Chen, Mingyi
AU - Huang, Eric C
AU - Chen, Xinbin
PY - 2018/3/15
Y1 - 2018/3/15
N2 - Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often altered in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice by shortening lifespan, altering tumor incidence, and promoting T-cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T-cell development. Furthermore, Rbm38 was required for Pten expression via stabilization of Pten mRNA through an AU-rich element in its 3'UTR. Our results suggest that Rbm38 controls T-cell lymphomagenesis by jointly modulating mutant p53 and Pten, with possible therapeutic implications for treating T-cell malignancies. Significance: An RNA-binding protein controls T-cell lymphomagenesis by jointly modulating mutant p53 and PTEN, with possible therapeutic implications for treating T-cell malignancies.
AB - Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often altered in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice by shortening lifespan, altering tumor incidence, and promoting T-cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T-cell development. Furthermore, Rbm38 was required for Pten expression via stabilization of Pten mRNA through an AU-rich element in its 3'UTR. Our results suggest that Rbm38 controls T-cell lymphomagenesis by jointly modulating mutant p53 and Pten, with possible therapeutic implications for treating T-cell malignancies. Significance: An RNA-binding protein controls T-cell lymphomagenesis by jointly modulating mutant p53 and PTEN, with possible therapeutic implications for treating T-cell malignancies.
UR - http://www.scopus.com/inward/record.url?scp=85047754584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047754584&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-17-2457
DO - 10.1158/0008-5472.CAN-17-2457
M3 - Article
VL - 78
SP - 1511
EP - 1521
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 6
ER -