journal contribution
posted on 2023-03-31, 01:27 authored by Jin Zhang, Enshun Xu, Cong Ren, Hee Jung Yang, Yanhong Zhang, Wenqiang Sun, Xiangmudong Kong, Weici Zhang, Mingyi Chen, Eric Huang, Xinbin Chen Supplemental Fig. S1 represents analysis of TLBL. Supplemental Fig. S2 contains representative images of H.E.-stained tumors. Supplemental Fig. S3 contains RT-PCR analysis of various genes (Tbet, NFAT1,NFAT2, IFNG, IL6) in thymus and TLBLs. Supplemental table S1-4 contains gender, survival, and tumor information of the mice.
Funding
American Cancer Research Institutional Research Grant
NIH
History
ARTICLE 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. Cancer Res; 78(6); 1511–21. ©2018 AACR.
